Targets Associated to Immuno Processes - Cytokine production & signalling
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| Cytokine production & signalling | Download as CSV | |||
Targets Associated to Immuno Processes
Full documentation can be found in the GtoImmuPdb immuno cell type data documentation (PDF). ✖ |
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| GPCRs | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| 5-HT2B receptor (5-Hydroxytryptamine receptors) |
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The expression of 5-HT2B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [579] ... | ||
| ACKR1 (Chemokine receptors) |
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ACKR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Studies in ACKR1 null mice, and analysis of ACKR1 SNPs in asthmatic patients with poorly controlled symptoms, suggest a role for this cytokine receptor in the temporal regulation of asthma pathophysiology and symptoms [96] ... | ||
| ACKR2 (Chemokine receptors) |
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ACKR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| ACKR3 (Chemokine receptors) |
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ACKR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. ACKR3 binds the chemokine CXCL12 (stromal cell-derived factor 1, SDF-1 which is also a ligand for CXCR4). ACKR3 is an atypical receptor in that it does not activate G-protein-mediated signaling but induces β-arrestin recruitment [261] ... | ||
| ACKR4 (Chemokine receptors) |
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ACKR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| ADGRG1 (Adhesion Class GPCRs) |
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An association between ADGRG1 and the tetraspanin CD81, negatively regulates the immediate effector functions (inflammatory cytokine and cytolytic protein production, degranulation, target cell killing) of mature NK cells [93] ... | ||
| A2B receptor (Adenosine receptors) |
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A2B receptor is discussed in this immuno-oncology review [3] ... | ||
| C3a receptor (Complement peptide receptors) |
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Complement C3a receptor 1 is the receptor for complement factor C3a, a component of the alternative complement cascade. It can have pro-inflammatory actions, but can also counteract the proinflammatory effects of C5a. The complement system plays a critical role intestinal immune homeostasis. In particular, C3 and the C3aR have been identified as being involved in regulating the intestinal immune response during chronic colitis [534,592] ... |
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| C5a1 receptor (Complement peptide receptors) |
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C5aR is typically associated with the compement cascade and innate immunity. MorphoSys have an anti-C5aR monoclonal antibody (MOR210; TJ210) in preclinical development as an immuno-oncology agent. The goal of anti-C5aR therapy is to reduce the effects that activation of the C5a/C5aR axis has on promoting cancer cell migration and invasiveness [235,344,400-401] ... |
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| C5a2 receptor (Complement peptide receptors) |
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C5aR is typically associated with the compement cascade and innate immunity. However, the complement C5a receptor 2 may act as a decoy receptor for C5a, as it has no reported G protein signalling capacity. | ||
| CCR1 (Chemokine receptors) |
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CCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CCR10 (Chemokine receptors) |
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CCR10 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CCR2 (Chemokine receptors) |
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CCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR2 is discussed in relation to immuno-oncology in [3] ... | ||
| CCR3 (Chemokine receptors) |
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CCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CCR4 (Chemokine receptors) |
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CCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. In disease states CCR4 is involved in recruiting T helper type 2 cell (Th2) subsets in autoimmune disorders such as asthma, allergic rhinitis, and atopic dermatitis [510] ... |
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| CCR5 (Chemokine receptors) |
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CCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR5 is discussed in relation to immuno-oncology in [3] ... | ||
| CCR6 (Chemokine receptors) |
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CCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. CCR6 is expressed on a variety of immune cells including memory and regulatory T-cells [277,325] ... | ||
| CCR7 (Chemokine receptors) |
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CCR7 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CCR8 (Chemokine receptors) |
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CCR8 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CCR9 (Chemokine receptors) |
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CCR9 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Activation of CCR9 by CCL25 plays a key role in leukocyte recruitment to the gut and CCR9 antagonists are being pursued as therapeutic agents for inflammatory bowel disease [593] ... | ||
| CCRL2 (Chemokine receptors) |
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CCRL2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. However, the nomenclature of CCLR2 for this receptor and its classification as a member of the chemokine receptor family is prov ... | ||
| chemerin receptor 1 (Chemerin receptors) |
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Studies in CMKLR1 (chemerin receptor 1) knockout mice highlight the role of this receptor in inflammation and obesity. Chemerin receptor 1 is activated by the lipid-derived, anti-inflammatory autacoid ligand resolvin E1. As its name suggests, reslovin E1 is involved in resolving physiological inflammatory responses. The metabolically stable resolvin E1 analogue, RX-10045 (navamepent) has completed Phase 2 clinical trials in several occular inflammation indications. In relation to multiple sclerosis (MS), clinical EAE is significantly reduced in CMKLR1 KO mice. Taking this in to consideration with data that confirm CMKLR1 expression by the main effector cells in MS, this protein is judged to be a novel and tractable target for therapeutic intervention in MS. CMKLR1 antagonists are being pursued as anti-inflammatory agents. The selective CMKLR1 antagonist CCX832 was developed by ChemoCentryx and GlaxoSmithKline as a potential anti-psoriatic medication, but development appears to have halted at Phase 1. |
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| CXCR1 (Chemokine receptors) |
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CXCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR1 is discussed in relation to immuno-oncology in [3] ... | ||
| CXCR2 (Chemokine receptors) |
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CXCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR2 is discussed in relation to immuno-oncology in [3] ... | ||
| CXCR3 (Chemokine receptors) |
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CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes. In the cancer setting cytokines are known to establish an immunosuppressive milieu that is condusive to tumour progression. CXCR3 and its ligands have specifically been identified as being associated with this mechanism in pancreatic ductal adenocarcinoma [79] ... |
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| CXCR4 (Chemokine receptors) |
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CXCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Due to its role in cancer cell homing and metastasis the CXCR4-CXCL12 axis is a potential target for cancer therapy [455,483,574,584] ... | ||
| CXCR5 (Chemokine receptors) |
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CXCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CXCR6 (Chemokine receptors) |
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CXCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR6 is upregulated by IL-2 and IL-15 [560] ... | ||
| CX3CR1 (Chemokine receptors) |
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CX3CR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| D2 receptor (Dopamine receptors) |
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D2 receptor-mediated anti-inflammatory effects in the kidney have a protective effect. In contrast, impaired D2 receptor function results in renal inflammation and organ damage [634] ... | ||
| EP4 receptor (Prostanoid receptors) |
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The EP4 prostanoid receptor is one of four receptor subtypes for prostaglandin PGE2. The anti- and pro-inflammatory (and non-inflammatory) activities of this receptor are reviewed in [618] ... | ||
| FFA1 receptor (Free fatty acid receptors) |
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Studies in Ffar1 (Gpr40) knockout mice indicate that it plays a protective role in fibrotic kidney disease models [176] ... | ||
| FFA2 receptor (Free fatty acid receptors) |
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FFAR2 is a GPCR activated by short-chain fatty acids, and evidence suggests that FFAR2 (and FFAR3) mediate beneficial effects associated with a fiber-rich diet. These GPCRs are of interest as targets for the treatment of inflammatory and metabolic diseases. FFAR2 is included in GtoImmuPdb as it is highly expressed on immune cells, in particular neutrophils, and evidence points to a role in diseases with dysfunctional neutrophil responses, such as inflammatory bowel disease (IBD). A Phase 2 trial of the clinical candidate GLPG0974 in ulcerative colitis has been completed (see NCT0182932). In vitro and in vivo studies suggest that the short-chain fatty acid/FFAR2 axis is modulated by metabolites of cholera toxin, that are produced by gut microbiota, which leads to enhanced mucosal antibody responses against enteric pathogen infection [612] ... |
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| FFA3 receptor (Free fatty acid receptors) |
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FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [65] ... | ||
| FFA4 receptor (Free fatty acid receptors) |
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FFA4 has been identified as a drug target in asthma and COPD [448] ... | ||
| GPR35 (Class A Orphans) |
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GPR35 is expressed by dendritic cells, macrophages, and granulocytes, all of which show chemotactic response to CXCL17 [437] ... | ||
| PAF receptor (Platelet-activating factor receptor) |
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PAF deficiency results in defective inflammatory response to infection in mice. | ||
| PAR1 (Proteinase-activated receptors) |
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PAR1 has been found to mediate the effects of neutrophil elastase (NE) on γδ T cell activation, as the PAR1 inhibitor |
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| PAR2 (Proteinase-activated receptors) |
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PAR2 receptors have been reported to elicit pain and inflammation through a neurogenic mechanism of action, causing release of substance P, activation of NK1 receptors, and sensitization of TRPV1 voltage-gated ion channels. This action can be negated using a selective NK1 receptor antagonist (L732,138) or a TRPV1 receptor antagonist (capsazepine) [181] ... | ||
| S1P3 receptor (Lysophospholipid (S1P) receptors) |
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| XCR1 (Chemokine receptors) |
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XCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. XCR1 is expressed by a subset of dendritic cells [311] ... | ||
| Ion Channels | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| nicotinic acetylcholine receptor α7 subunit (Nicotinic acetylcholine receptors (nACh)) |
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Included in Guide to Immunopharmacology as CHRNA7 knockout aggravates rheumatoid arthritis in mice [564] ... | ||
| P2X7 (P2X receptors) |
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The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [328,457] ... | ||
| TRPM4 (Transient Receptor Potential channels (TRP)) |
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TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [424] ... | ||
| TRPV1 (Transient Receptor Potential channels (TRP)) |
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Several lines of evidence suggest that TRPV1 is implicated in some inflammatory processes [25,46,339,346,481] ... | ||
| TRPV4 (Transient Receptor Potential channels (TRP)) |
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Expressed on mouse neutrophils [424] ... | ||
| Nuclear Hormone Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| Farnesoid X receptor (1H. Liver X receptor-like receptors) |
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FXR is predominantly expressed in liver, intestine, kidney and adipose tissue, but has also been detected in immune cells (CD4+, CD8+, CD19+ and CD14+ cells) [489] ... | ||
| Liver X receptor-α (1H. Liver X receptor-like receptors) |
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Liver X receptors (LXR) are involved in the regulation of lipid metabolism and inflammatory responses. As such they are novel drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with potential therapeutic effects in neurodegenerative diseases [605] ... | ||
| Liver X receptor-β (1H. Liver X receptor-like receptors) |
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Liver X receptors are involved in the regulation of lipid metabolism and inflammatory responses. LXRs are drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with therapeutic potential in neurodegenerative diseases [605] ... | ||
| Peroxisome proliferator-activated receptor-γ (1C. Peroxisome proliferator-activated receptors) |
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PPARγ agonists have anti-inflammatory effects. Full PPARγ agonists can cause undesireable weight gain, but partial agonists are devoid of this adverse effect and retain the anti-inflammatory effects of PPARγ modulation. The PPARγ agonist |
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| Retinoic acid receptor-γ (1B. Retinoic acid receptors) |
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Retinoid drugs reduce the proinflammatory factors and disrupt the immunoinflammatory cascade associated with acne vulgaris. RARγ is one of the molecular targets of anti-acne retinoid family drugs. RARγ-selective retinoid derivatives are being investigated as topical agents, which are exp ... | ||
| Enzymes | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| 5-LOX (Lipoxygenases) |
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5-LOX is included in GtoImmuPdb because of its involvement in eicosanoid turnover and because it is being actively pursued as a molecular target for the development of novel anti-inflammatory therapeutics [506] ... | ||
| ABL proto-oncogene 1, non-receptor tyrosine kinase (Abl family) |
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Included in GtoImmuPdb based on its association with leukemia. | ||
| aconitate decarboxylase 1 (Itaconate biosynthesis) |
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Itaconate (itaconic acid) is generated from the citric acid (TCA) cycle intermediate cis-aconitic acid which is produced by mitochondria. Itaconate is synthesised by the enzyme aconitate decarboxylase 1 (referred to as immunoresponsive gene 1 or IRG1). Its synthesis links metabolism to immunity and it plays an important role in the macrophage-based immune response [115,147] ... | ||
| ADAM10 (M12: Astacin/Adamalysin) |
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ADAM10 has been identified as the primary physiologically relevant sheddase responsible for cleavage of |
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| ADAM17 (M12: Astacin/Adamalysin) |
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The proteolytic activity of ADAM17 (a type I transmembrane metalloproteinase; a.k.a.TNF-alpha converting enzyme or TACE) is involved in the shedding of the extracellular domains of several transmembrane proteins e.g. cytokines (TNFα), growth factors, receptors (IL-6R and TNF-R for example) and adhesion molecules. Cleavage of substrates, including TNFα, IL-6R and L-selectin, produce pro-inflammatory effects stimulating both innate and acquired immune responses. ADAM17 activity is crucial during development (ADAM17 knockout is embryonic lethal), and it has been shown that the soluble IL-6R/IL-6 complex generates agonist-like signals in a process termed IL-6 trans-signaling. The generation and maintenance of several inflammatory and autoimmune diseases is driven by IL-6 trans-signaling [90] ... | ||
| ADAM8 (M12: Astacin/Adamalysin) |
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ADAM8 is reported to drive acute allergen-induced airway inflammation in a mouse model, and effect negated by ADAM8-deficiency (antibody-induced or gene knockout) [431] ... | ||
| Arginase I (Arginase) |
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The role of ARG1 in immuno-oncology is reviewed in [3] ... | ||
| Arginase II (Arginase) |
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The role of ARG2 in immuno-oncology is reviewed in [3] ... | ||
| Bruton tyrosine kinase (Tec family) |
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The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [44] ... | ||
| casein kinase 2, beta polypeptide subunit (Casein kinase 2 (CK2) family) |
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CSNK2B is included in Guide to IMMUNOPHARMACOLOGY as it is a subunit of the casein kinase 2 complex. | ||
| Caspase 1 (C14: Caspase) |
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Caspase 1 is also known as interleukin-1beta (IL-1α) converting enzyme (ICE). Amongst its substrates are the precursors of the inflammatory cytokines IL-1β and IL-18, which it proteolytically cleaves into active mature peptides. | ||
| Caspase 3 (C14: Caspase) |
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Defective caspase 3 expression in immune effector cells may influence susceptibility to Kawasaki disease, an acute vasculitis syndrome affecting small- and medium-sized arteries of infants and children [416] ... | ||
| Caspase 4 (C14: Caspase) |
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Recognition of cytoplasmic lipopolysaccharide (LPS) by Inflammatory caspases including caspases-4 and -5 leads to pyroptosis and secretion of inflammatory mediators [500-501] ... | ||
| Caspase 8 (C14: Caspase) |
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Roles of apoptotic caspases extending beyond cell death, for example, mediating cellular immune processes such as inflammasome modulation, necroptosis and pro-inflammatory cytokine processing have been reported [347] ... | ||
| cathepsin G (S1: Chymotrypsin) |
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Cathepsin G is a leukocyte serine protease of the chymotrypsin family, related to neutrophil elastase and the granzymes. It is stored in azurophil granules and acts intracellularly to degrade ingested host pathogens and axtracellularly to breakdown ECM components at sites of inflammation. Cathepsin ... | ||
| chitinase acidic (Chitinases) |
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AMCase has been shown to be produced during type 2 inflammatory responses [639] ... | ||
| chymase 1 (S1: Chymotrypsin) |
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Chymase is a chymotrypsin-like serine protease that is expressed by mast cells. Amongst its activities, chymase is involved in the conversion of angiotensin (AT) I to ATII, its protease activity cleaves latent TGFβ1 and IL-1β in the cellular environment to generate the active cytokines, and it can further stimulate mast cell degranulation in a self-amplification loop. The potential of chymase as a drug target for inflammatory and gastrointestinal disorders is reviewed by Heuston and Hyland (2012) [224] ... | ||
| component of inhibitor of nuclear factor kappa B kinase complex (IKK family) |
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Ikkα is one of the catalytic subunits of the IκB kinase (IKK) complex, an upstream component of the NF-κB signal transduction cascade; NF-κB signaling being involved in propagating the cellular response to inflammation. IKK frees NF-κB from its inhibitory interaction with IκBα (inhibitor of kappa B), allowing NF-κB translocation to the nucleus where it modulates transcriptional activity. Additional functions of Ikkα beyond NF-κB activation are reviewed in [236] ... | ||
| COX-2 (Cyclooxygenase) |
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The cyclooxygenase enzymes are included in GtoImmuPdb as they are involved in the production of inflammatory mediators, and are long-standing anti-inflammatory drug targets. The role of COX-2 in immuno-oncology is reviewed in [3] ... | ||
| C-terminal Src kinase (Csk family) |
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CSK is an inhibitory regulator of Src family kinases, a family of protein tyrosine kinases indispensable to the initiation of signal transduction via ITAM-bearing immunoreceptors, and cytokine, growth factor, and pattern recognition receptor signalling. CSK phosphorylates an inhibitory tyrosine residue at the C terminus of Src kinases, leading to autoinhibition. CSK-induced Src kinase inhibition can also be mediated by binding to PEST family receptor tyrosine phosphatases [567] ... | ||
| Cyclic GMP-AMP synthase (Cyclic GMP-AMP synthase) |
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Cyclic GMP-AMP synthase (cGAS) directly binds to cytosolic DNA, and in response catalyses the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Thus cGAS acts as a sensor of DNA in the cytoplasm, which is an indicator of pathogen invasion [530] ... | ||
| dual oxidase 1 (NADPH oxidases) |
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DUOX1 participates in innate immune responses to epithelial injury and allergens, and in the development of allergic diseases [563] ... | ||
| elastase, neutrophil expressed (S1: Chymotrypsin) |
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Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host extracellular matrix, such as collagen-IV and elastin, hence its role in degenerative and inflammatory diseases. NE functions as a promoter of γδ T cell activation via a protease-activated receptor (PAR1)-dependent mechanism [551] ... | ||
| enhancer of zeste 2 polycomb repressive complex 2 subunit (2.1.1.43 Histone methyltransferases (HMTs)) |
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EZH2 is involved in hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis, with notable participation in regulating the differentiation and function of T cells. This role suggests potential applications in immune-mediated conditions, including autoimmune disorders [553] ... | ||
| eukaryotic translation initiation factor 2 alpha kinase 2 (Other PEK family kinases) |
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Protein kinase-R (EIF2AK2) is activated by virally-introduced double-stranded RNA (dsRNA), and is therefore involved in protection against viral infection. Protein activator of the interferon-induced protein kinase EIF2AK2 (PACT; PRKRA) also activates protein kinase-R. Activated protein kinase-R phosphorylates the eukaryotic translation initiation factor eIF2α inhibiting viral protein synthesis [180] ... | ||
| FER tyrosine kinase (Fer family) |
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FER acts downstream of the activated high affinity immunoglobulin epsilon receptor (FCεR1) and plays a role in FCεR1-mediated signaling in mast cells, regulation of mast cell degranulation, leukocyte recruitment, and leukocyte extravasation following bacterial lipopolysaccharide (LPS ... | ||
| FGR proto-oncogene, Src family tyrosine kinase (Src family) |
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Fgr may be involved in neutrophil migration, potentially via binding to intergrins [38] ... | ||
| glycogen synthase kinase 3 beta (GSK subfamily) |
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GSK3β plays an essential function in T cell differentiation and proliferation, and its activity is inhibited following antigen-driven T cell activation [51-52,337,412] ... | ||
| Haem oxygenase 1 (Haem oxygenase) |
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Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme, catalyzing the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO). Heme oxygenase 1 (HO1) is a Nrf2-regulated gene, whose expression is upregulated as a cytoprotective mechanism in response to cellular stresses including inflammation, ischemia, hypoxia, hyperoxia, hyperthermia, or radiation. HO1 has antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, playing an important role in the prevention of vascular inflammation and atherogenesis (reviewed in [24] ... |
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| HCK proto-oncogene, Src family tyrosine kinase (Src family) |
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Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [38] ... | ||
| heparanase (3.2.1.- Glycosidases) |
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Heparanase has been studied as a novel drug target associated with the immune response and inflammation [94-95] ... | ||
| IL2 inducible T cell kinase (Tec family) |
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The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [44] ... | ||
| indoleamine 2,3-dioxygenase 1 (1.13.11.- Dioxygenases) |
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The indoleamine 2,3 dioxygenase (IDO) branch of the kynurenine (KYN) pathway of tryptophan metabolism has been intensely studied in relation to immune tolerance and allergy. IDO is generally considered to be a tolerogenic, immunosuppressive enzyme, that is induced by IFN-γ. It provides a negative feedback pathway that limits uncontrolled immune responses. Its immunosuppressive actions arise from its promotion of tryptophan depletion, and elevation of KYN metabolite levels. The aryl hydrocarbon receptor serves as a receptor for KYN and should be considered when evaluating the IDO-KYN pathway in immune homeostasis and its potential to modulate innate and adaptive immune responses [278] ... | ||
| Inducible NOS (Nitric oxide synthases) |
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The role of iNOS in immuno-oncology is reviewed in [3] ... | ||
| inhibitor of nuclear factor kappa B kinase subunit beta (IKK family) |
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Iκβ kinase β (IKK-2) is the pivotal enzyme component of the Iκβ kinase (IKK) complex, a complex crucial in regulating expression and activation of inflammatory mediators in airway epithelium. IKK-2 is an attractive target for development of pharmaceutical inhibitors with antiinflammatory action as treatments for asthma and chronic obstructive pulmonary disease (COPD) [40,57,512] ... | ||
| inhibitor of nuclear factor kappa B kinase subunit epsilon (IKK family) |
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IKKε is the only inducible IKK family member. Expression is induced in response to LPS, viral infection and several cytokines. IKKε expression is restricted to pancreas, thymus, spleen and peripheral blood leukocytes. This is in contrast to all other IKK family kinases which are cons ... | ||
| INPP5D (Inositol polyphosphate phosphatases) |
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SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [398,525] ... | ||
| interleukin 1 receptor associated kinase 1 (Interleukin-1 receptor-associated kinase (IRAK) family) |
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One of the two proximal mediators of IL-1 signaling via the IL-1 receptor, plays a part in IL-1-induced upregulation of the transcription factor NF-κB, the other being IRAK2. Interacts with other proteins including TRAF6, Myd88, CHUK, IKK2 and TLR4. | ||
| interleukin 1 receptor associated kinase 2 (Interleukin-1 receptor-associated kinase (IRAK) family) |
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IRAK2 is one of the proximal mediators of IL-1 signalling via the IL-1 receptor, the other being IRAK1. It plays a part in IL-1-induced upregulation of the transcription factor NF-κB. IRAK2 interacts with TRAF6 and Myd88. | ||
| interleukin 1 receptor associated kinase 3 (Interleukin-1 receptor-associated kinase (IRAK) family) |
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IRAK3 expression is restricted to monocytes and macrophages. | ||
| interleukin 1 receptor associated kinase 4 (Interleukin-1 receptor-associated kinase (IRAK) family) |
IRAK4 is involved in Myddosome formation which regulates transcription factor activation and drives cytokine production to effect anti-pathogen responses and inflammation [154,389]. |
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IRAK4 is essential for most innate immune responses to bacteria and viruses, and IRAK4 deficiency (caused by mutations) has been shown to result in recurrent invasive pneumococcal disease [364] ... | |
| Janus kinase 1 (Janus kinase (JakA) family) |
JAK1 is crucial for mediating the intracellular signals for a range of type I and type II cytokines, and for type I and type II interferons (IFN-α/β and IFN-γ respectively) following ligand-receptor interaction. |
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The JAK1 tyrosine kinase is crucial for signaling of certain type I and type II cytokines, via receptors belonging to the IL-2, IL-4 and IL-6 receptor families as well as neurotrophin-1 and leptin receptors (all type I cytokine receptors). JAK1 is also involved in signalling via type I ... | |
| Janus kinase 2 (Janus kinase (JakA) family) |
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JAK2 signal transduction is a critical mediator of the immune response and is implicated in autoimmune conditions and in graft-versus-host disease (GvHD). The pro-inflammatory effects of IL-6, IL-12, and IL-23 on T cells are mediated via JAK2 [48,50,520] ... | ||
| Janus kinase 3 (Janus kinase (JakA) family) |
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Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [18] ... | ||
| kynurenine 3-monooxygenase (1.14.13.9 Kynurenine 3-monooxygenase) |
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GSK180-induced inhibition of KMO prevents multiple organ failure in rodent models of acute pancreatitis which is caused by excessive alcohol consumption [372] ... | ||
| LYN proto-oncogene, Src family tyrosine kinase (Src family) |
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LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [171,179,550] ... | ||
| mitogen-activated protein kinase 1 (ERK subfamily) |
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In endothelial cells of the vasculature, and in activated human mast cells, ERK serves as an anti-inflammatory signal that suppresses production of pro-inflammatory mediators [273,345] ... | ||
| mitogen-activated protein kinase 11 (p38 subfamily) |
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p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [204-205,301,432,453,582] ... | ||
| mitogen-activated protein kinase 13 (p38 subfamily) |
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p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [204-205,301,432,453,582] ... | ||
| mitogen-activated protein kinase 14 (p38 subfamily) |
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p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [204-205,301,432,453,582] ... | ||
| mitogen-activated protein kinase kinase kinase 5 (STE11 family) |
|
ASK1 is included in the GToImmuPdb as it is a molecular target for anti-fibrotic drug development. This kinase acts upstream of p38 MAPK and JNK kinases [241] ... | ||
| mitogen-activated protein kinase kinase kinase 7 (TAK1 subfamily) |
|
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [130,479] ... | ||
| mitogen-activated protein kinase kinase kinase kinase 3 (KHS subfamily) |
|
GLK (KHS2; MAP4K3) is ubiquitously expressed. It is involved in cellular responses to stress and inflammation [145] ... | ||
| MMP12 (M10: Matrix metallopeptidase) |
|
MMP12 is included in GtoImmuPdb based on its reported involvement in asthma and potential as a asthma therapeutic target. | ||
| MMP2 (M10: Matrix metallopeptidase) |
|
MMP2 is included in GtoImmuPdb based on its potential involvement in asthma. | ||
| MMP8 (M10: Matrix metallopeptidase) |
|
MMP8 is included in GtoImmuPdb based on its potential protective role in asthma. | ||
| otulin (C101: OTULIN peptidase) |
|
Otulin is reported as a negative regulator of inflammation and autoimmunity [132] ... | ||
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
|
PI3Kδ is preferentially expressed in cells of hemopoietic lineage and is involved in neutrophil chemotaxis. It is the only PI3K isoform with expression restricted to leukocytes. Genetic and pharmacological inactivation of PI3Kδ indicates its importantance for the function of T cells, B cell, mast cells and neutrophils. PI3kδ is a promising target for drugs for preventing or treating inflammation, autoimmunity and transplant rejection [212] ... | ||
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
|
The role of PI3Kγ in immuno-oncology is reviewed in [3] ... | ||
| phosphodiesterase 4B (Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs)) |
|
PDE4 is a drug target, whose inhibition has anti-inflammatory action. PDE4 inhibitors have already entered clinical use, being employed in the treatment of inflammatory skin conditions such as psoriatic arthritis ( |
||
| phosphodiesterase 4D (Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs)) |
|
The selective PDE4 inhibitor |
||
| phosphoinositide-3-kinase regulatory subunit 1 (Phosphatidylinositol kinases) |
|
p85α is included in GtoImmuPdb as it is the regulatory subunit of several PI3Ks (e.g. PI3Kδ and PI3Kγ) with roles in leukocyte biology and therefore important for immunity [341] ... | ||
| PLCγ2 (Phosphoinositide-specific phospholipase C) |
|
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [187,478] ... | ||
| protein kinase C alpha (Delta subfamily) |
|
PKCα is included in GtoImmuPdb based on its GO immune process associations. | ||
| protein kinase C iota (Iota subfamily) |
|
PKCι is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes. | ||
| protein kinase C theta (Delta subfamily) |
|
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [29] ... | ||
| protein kinase C zeta (Iota subfamily) |
|
PKCζ is included in GtoImmuPdb based on its GO process associations. | ||
| protein tyrosine kinase 2 beta (Fak family) |
|
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific (e.g. chemokine and integrin receptors) T cell development and activation [97] ... | ||
| protein tyrosine phosphatase non-receptor type 11 (Protein tyrosine phosphatases non-receptor type (PTPN)) |
|
SHP2 regulates programmed cell death 1 (PD-1)-mediated signal transduction and it is therefore involved in immune checkpoint modulation. | ||
| protein tyrosine phosphatase non-receptor type 22 (Protein tyrosine phosphatases non-receptor type (PTPN)) |
|
PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [113] ... | ||
| receptor interacting serine/threonine kinase 1 (Receptor interacting protein kinase (RIPK) family) |
|
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [395,463,504,573] ... | ||
| receptor interacting serine/threonine kinase 2 (Receptor interacting protein kinase (RIPK) family) |
|
RIPK2 is involved in innate immune responses, mediating pro-inflammatory signaling from the bacterial peptidoglycan-sensing NOD1/NOD2 subfamily of innate immune pattern recognition receptors (PRRs) and signalling downstream from the Toll-like receptor (TLR) family of PRRs. Further evidence suggesting an inflammatory role is the targeting of RIPK2 (along with RIPK1/3) by the IAP family E3 ubiquitin ligases (enzymes playing a critical role in innate immunity) [408] ... | ||
| receptor interacting serine/threonine kinase 3 (Receptor interacting protein kinase (RIPK) family) |
|
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [395,463,504,573] ... | ||
| Rho associated coiled-coil containing protein kinase 2 (Rho kinase) |
|
ROCK2 plays a role in controlling T-cell plasticity and macrophage polarization, skewing polarization towards M1-type macrophages [627] ... | ||
| sirtuin 1 (3.5.1.- Histone deacetylases (HDACs)) |
|
Sirtuin 1 has been suggested as a molecular target for host-directed therapy against Mycobacterium tuberculosis infection by research that shows that activation of sirtuin 1 decreases lung pathology, reduces inflammation, and enhances drug efficacy against Mycobacterium tuberculosis [104] ... | ||
| sphingosine kinase 1 (Sphingosine kinase) |
|
The sphingosine kinases (SPHK1 and SPHK2; SK1, SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. SK1-selective inhibitors include PF-543 [486-487] ... | ||
| sphingosine kinase 2 (Sphingosine kinase) |
|
The sphingosine kinases (SPHK1 and SPHK2; SK1, SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling, and is considered to be an anti-inflammatory enzyme with potential druggability for the treatment of autoimmune and inflammatory diseases [451] ... | ||
| sPLA2-1B (Phospholipase A2) |
|
sPLA2 enzymes catalyze the first step of the arachidonic acid pathway, so are inextricably involved in the production of arachadonic acid for inflammatory mediator synthesis. Excess sPLA2 activity is suggested to contribute to several inflammatory diseases. The sPLA2-1B isozyme has been reported to induce leukotriene B4 (LTB4) production in human neutrophils, using a mechanism independent of arachadonic acid generation [298] ... | ||
| spleen associated tyrosine kinase (Syk family) |
|
SYK plays a key role in coupling activated immunoreceptors to downstream cellular responses such as proliferation, differentiation, and phagocytosis. Mast cell, macrophage and B-cell activation (and release of inflammatory modulators) is disrupted by inhibition of SYK-mediated immunoreceptor signalling. Selective SYK inhibitors are being sought for a number of inflammatory conditions including rheumatoid arthritis, B-cell lymphoma and asthma/rhinitis [186,461] ... | ||
| SRC proto-oncogene, non-receptor tyrosine kinase (Src family) |
|
Src family tyrosine kinases act as general modulators of immune cell signaling, playing diverse signaling functions, both inhibitory and stimulatory, in immunoreceptor and integrin signaling pathways [338] ... | ||
| TANK binding kinase 1 (IKK family) |
|
TBK1 belongs to the IKK-kinase family of enzymes. It is a ubiquitously expressed serine/threonine protein kinase, and constitutes a key regulatory node for several signaling pathways involved in the innate immune response that lead to induction of type I interferons. Several classes of innate sensors including the TLRs and retinoic acid-inducible gene 1 (RIG-I)-like helicases engage TBK1-IRF3 signaling pathways to regulate transcription of type I IFNs. In neuroinflammation TBK1 is involved in TLR-dependent [267] ... | ||
| tripartite motif containing 21 (2.3.2.27 RING-type E3 ubiquitin transferase) |
|
Tripartite motif-containing (TRIM) superfamily proteins are critical in a variety of biological processes in innate immunity and are important for eradication of invading pathogens [419,454,569] ... | ||
| tripartite motif containing 38 (2.3.2.27 RING-type E3 ubiquitin transferase) |
|
TRIM38 catalyses the ubiquitination of Lys48 of the Toll-like receptor (TLR) adaptor protein TICAM1 (commonly referred to as TRIF) which mediates its proteosomal degradation. This action has been shown to inhibit TLR3-driven type I interferon signaling of the innate immune response [606] ... | ||
| TXK tyrosine kinase (Tec family) |
|
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [44] ... | ||
| tyrosine kinase 2 (Janus kinase (JakA) family) |
|
TYK2 was the first member of the Janus kinase family to be identified. It associates with the cytoplasmic domain of type I and type II cytokine receptors, where it phosphorylates receptor subunits and facilitates signalling downstream of the receptors for the p40-containing cytokines IL-12 and IL-23 via activation of STAT-dependent transcription factors. It also mediates Type I IFN-driven responses [523] ... | ||
| Catalytic Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| AXL receptor tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
|
All three TAM family receptor tyrosine kinases are involved in regulating inflammatory responses through a negative feedback loop. Specifically, AXL-Gas6 signalling is reported to induce autophagy in murine macrophages via inhibition of the NLRP3 inflammasome, an effect which reduces hepatic inflammation in a mouse model [203] ... | ||
| BAFF receptor (Tumour necrosis factor (TNF) receptor family) |
|
This is a type III membrane bound receptor for B cell activating factor (BAFF). BAFF enhances B cell survival and hence regulates the peripheral B cell population. It is suggested that overproduction of BAFF may enhance the survival of autoreactive B cells, an effect which may contribute in the path ... | ||
| B cell maturation antigen (Tumour necrosis factor (TNF) receptor family) |
|
B-cell maturation antigen (BCMA) is a cell surface receptor for B-cell activating factor (BAFF). It interacts with various TRAF family adaptor proteins to modulate cell survival and proliferation, via NF-κB and MAPK8/JNK signal transduction pathways. BCMA is highly plasma cell-selective for malignant plasma cells from multiple myeloma (MM) patients, and is being investigated as a target for therapies to tackle relapsed/refractory MM [220,307] ... | ||
| CD30 (Tumour necrosis factor (TNF) receptor family) |
|
Expressed by activated T and B cells. Interacts with TRAF2 and TRAF5 to elicit downstream signalling events (NF-κB activation). CD30 may protect against autoimmunity by limiting the proliferative potential of autoreactive CD8 effector T cells. CD30 is the target of the approved anti-lymphoma monoclonal antibody drug brentuximab vedotin ... | ||
| CD40 (Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family) |
|
CD40 is a stimulatory receptor and a member of the tumor necrosis factor receptor superfamily (TNFRSF). It is expressed on a variety of immune cells, including macrophages, B cells, and dendritic cells (DCs). CD40 plays a key role in the activation of the immune system. Endogenous ligand is CD154 (C ... | ||
| CIITA (NOD-like receptor family) |
|
CIITA is a transcriptional coactivator for the transcription factor RFX5 [488] ... | ||
| colony stimulating factor 1 receptor (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
|
Activation of the CSF1R induces myeloid proliferation, and in the tumour microenvironment this promotes M1 to M2 polarization and accumulation of tumour-associated macrophages (TAMs). The CSF1R is therefore being investigated as an immuno-oncology drug target [3] ... | ||
| Cytokine receptor common β subunit (IL-3 receptor family) |
|
This a signal transducing protein subunit shared by the functional receptor heterodimers for the cytokines IL-3, IL-5 and GM-CSF, with each receptor having a unique ligand binding alpha subunit. | ||
| Cytokine receptor-like factor 2 (IL-2 receptor family) |
|
Cytokine receptor-like factor 2 is the signal transducing subunit of the functional heterodimeric receptor for thymic stromal lymphopoietin (TSLP). Ligand binding is attributed to the interleukin-7 receptor subunit α. | ||
| death receptor 3 (Tumour necrosis factor (TNF) receptor family) |
|
In the absence of any other exogenous signals, activation of DR3 causes proliferation of FoxP3+ regulatory T cells [490] ... | ||
| death receptor 6 (Tumour necrosis factor (TNF) receptor family) |
|
Expressed predominantly in the thymus, spleen and white blood cells. May play a role in T helper cell activation, inflammation and immune regulation. Signals via the TRADD adaptor protein to the NF-κB and MAPK8/JNK pathways. | ||
| DExD/H-box helicase 58 (RIG-I-like receptor family) |
|
RIG-I is an intracellular sensor that responds to viral nucleic acids and activates downstream signaling, resulting in the induction of the type I interferon response [357] ... | ||
| DExH-box helicase 58 (RIG-I-like receptor family) |
|
LGP2 binds RNA but does not participate in the signaling pathway that RIG-1 and MDA5 are part of, and is assumed to provide a negative feedback for IFNβ induction by sequestering pathogen-derived RNA. | ||
| Eythropoietin receptor (Prolactin receptor family) |
|
A non-hematopoietic EPOR-containing receptor, called the innate repair receptor (IRR) or tissue-protective receptor, down-modulates the damaging effects of the immune response to tissue injury [62] ... | ||
| Fas (Tumour necrosis factor (TNF) receptor family) |
|
Fas receptor (CD95) is a cell surface protein that belongs to the tumor necrosis factor receptor family, that along with its ligand CD95L, generates a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. This system is also important in the immune elimination of virus-infected cells, cancer cells and autoreactive T cells. Mouse strains with mutations in Fas or CD95L develop lymphoproliferative conditions, indicating the importance of these proteins to immune cell homeostasis [536] ... | ||
| Fc fragment of IgE receptor Ig (Fc epsilon receptors) |
|
The FCER1G protein is a gamma subunit that is utilised as part of the high affinity IgE receptor (a key complex involved in mediating allergic reactions) and other Fc receptors. | ||
| fms related receptor tyrosine kinase 3 (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
|
FLT3 is the receptor for the cytokine Flt3 ligand (FLT3LG). Flt3 ligand is a growth factor akin to stem cell factor and colony stimulating factor 1, and is essential for hematopoietic progenitor cell development and expansion of both myeloid and lymphoid lineages. It is one of the growth factor receptors targeted by the chemotherapeutic tyrosine kinase inhibitor sorafenib. Results from mouse experiments suggest that Flt3 ligand is effective in treating sepsis, by potentiating innate immune functions of dendritic cells and neutrophils and improving T cell function [429] ... |
||
| glucocorticoid-induced TNF receptor (Tumour necrosis factor (TNF) receptor family) |
|
GITR appears to act as a co-stimulatory immune checkpoint molecule. T cell activation induces GITR expression. GITR inhibits the suppressive activity of Treg cells and promotes survival of Teff cells. | ||
| GM-CSF receptor, α subunit (IL-3 receptor family) |
|
This is the ligand binding subunit of the functional GM-CSF receptor complex. | ||
| Granulocyte colony-stimulating factor receptor (Prolactin receptor family) |
|
This nuclear receptor mediates the effects of the cytokine, colony stimulating factor 3 (CSF3). CSF3 regulates the production, differentiation, and function of granulocytes. | ||
| herpes virus entry mediator (Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family) |
|
HSV viral envelope glycoprotein D (gD) binds to this protein and thereby gains entry to the cell. HVEM binds to several TRAFadaptor proteins to mediate intracellular signalling and activation of the immune response. | ||
| integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor) (Integrins) |
|
Integrin subunit alpha 4 is the alpha subunit of the α4β1 lymphocyte homing receptor. The cytoplasmic domain of α4 binds tightly to paxillin, a signaling adaptor protein, and this interaction promotes increased cell migration and inhibits cell spreading [206] ... | ||
| interferon α/β receptor 1 (Interferon receptor family) |
|
IFNAR1 is a subunit of the functional receptor for type I interferons (NOT interferon γ). Type I interferons (IFN) exhibit an established anti-viral action. However, type I IFN signalling also appears to play a role in impaired resistance to a range of other pathogens (e.g. bacterial infection) [84,396] ... | ||
| Interferon α/β receptor 2 (Interferon receptor family) |
|
A subunit of the functional receptor for various interferons (NOT interferon γ). | ||
| Interferon γ receptor 1 (Interferon receptor family) |
|
A subunit of the functional receptor for interferon γ. | ||
| Interferon γ receptor 2 (Interferon receptor family) |
|
A subunit of the functional receptor for interferon γ. | ||
| interferon induced with helicase C domain 1 (RIG-I-like receptor family) |
|
MDA5 is an intracellualar RNA sensor. It recognizes longer double-stranded RNA sequences than RIG-1. In autoimmunity, MDA5 has been specifically linked with type I diabetes and anti-MDA5 autoantibodies can be detected in patients with certain connective tissue autoimmune conditions [6,232,369] ... | ||
| Interferon-λ receptor subunit 1 (IL-10 receptor family) |
|
Interferon-λ receptor subunit 1 is the ligand binding component of the functional heterodimeric receptor for interferons λ1, λ2 and λ3 | ||
| Interleukin 10 receptor, α subunit (IL-10 receptor family) |
|
Interleukin 10 receptor, α subunit is a component of the functional IL-10 receptor heterodimer. | ||
| Interleukin 10 receptor, β subunit (IL-10 receptor family) |
|
Interleukin 10 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 10 and 22 and for interferons λ1, λ2 and λ3. | ||
| Interleukin-11 receptor, α subunit (IL-6 receptor family) |
|
This is the ligand-binding component of the functional receptor for interleukin 11. | ||
| Interleukin-12 receptor, β1 subunit (IL-12 receptor family) |
|
This protein is a subunit of both the IL-12 and IL-23 cytokine receptors. | ||
| Interleukin-12 receptor, β2 subunit (IL-12 receptor family) |
|
This protein is a subunit of the functional receptor heterodimer for the IL-12 cytokine. | ||
| Interleukin 13 receptor, α2 (IL-2 receptor family) |
|
Interleukin 13 receptor, α2 acts as a high affinity decoy receptor for interleukin 13 that sequesters the ligand away from IL13Rα1 and is involved in down-regulating IL-13 responses in vivo. IL13ra2 null mice exhibit enhanced IL-13 responses [600] ... | ||
| Interleukin-13 receptor subunit α1 (IL-2 receptor family) |
|
Interleukin-13 receptor subunit α1 is a component of the functional receptors that mediate the pro-inflammatory actions of the cytokines IL-4 and IL-13. | ||
| Interleukin-15 receptor subunit α (IL-2 receptor family) |
|
This is the ligand binding subunit of the functional IL-15 receptor complex. | ||
| Interleukin 17 receptor A (IL-17 receptor family) |
|
This protein is a common subunit shared by the heterodimeric receptors for interleukins 17 (A, B , C and F) and 25. | ||
| Interleukin 17 receptor B (IL-17 receptor family) |
|
IL17RB is a subunit of the heterodimeric interleukin-25 receptor. | ||
| interleukin 17 receptor C (IL-17 receptor family) |
|
This is a subunit of the heterodimeric interleukin-17 receptor. | ||
| Interleukin-17 receptor D (IL-17 receptor family) |
|
IL17RD acts as an inhibitor of proinflammatory cytokine signaling (by limiting NF-κB translocation to the nucleus) [173] ... | ||
| Interleukin 17 receptor E (IL-17 receptor family) |
|
This is a component of the heterodimeric interleukin-17C receptor. | ||
| Interleukin-18 receptor 1 (Immunoglobulin-like family of IL-1 receptors) |
|
Interleukin-18 1 protein (IL18R1) is the ligand binding subunit of the functional IL-18 receptor heterodimer. | ||
| Interleukin-1 receptor-like 1 (Immunoglobulin-like family of IL-1 receptors) |
|
IL1RL1 (ST2) is the ligand binding subunit of the functional receptor for IL-33. It is mainly expressed on mast cells, eosinophils and other immune cells [178] ... | ||
| Interleukin-1 receptor-like 2 (Immunoglobulin-like family of IL-1 receptors) |
|
Interleukin-1 receptor-like 2 is one of the subunits of the functional receptor for IL-36. An antibody that mimics IL-36RA's antagonist activity at the IL-36 receptor (MAB92) has been described [177] ... |
||
| Interleukin 1 receptor, type I (Immunoglobulin-like family of IL-1 receptors) |
|
This is one of the subunits of the functional IL-1 receptor type I heterodimer. | ||
| Interleukin 1 receptor, type II (Immunoglobulin-like family of IL-1 receptors) |
|
IL-1R2 acts as a decoy receptor for IL-1β, thus reducing IL-1β binding/activation of IL-1R1. IL-1R2 thereby acts to down-regulate IL-1 responses [188,393] ... | ||
| Interleukin 20 receptor, α subunit (IL-10 receptor family) |
|
Interleukin 20 receptor, α subunit is a component of the functional receptor heterodimer for interleukin 20. | ||
| Interleukin 20 receptor, β subunit (IL-10 receptor family) |
|
Interleukin 20 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 19, 20 and 24. | ||
| Interleukin 21 receptor (IL-2 receptor family) |
|
This is the ligand binding subunit of the functional heterodimeric receptor for interleukin 21. | ||
| Interleukin 22 receptor, α1 subunit (IL-10 receptor family) |
|
IL22RA1 is a subunit in the heterodimeric receptors for interleukins 20 and 24 (which bind to the interleukin-22α1/20β heteromer) and IL-22 (which binds to the interleukin-22α1/10β heteromer). | ||
| Interleukin-22 receptor α2 (IL-10 receptor family) |
|
IL22RA2 (a.k.a. IL-22 binding protein) appears to act as a high affinity, soluble monomeric decoy receptor for IL-22 capable of neutralizeing the potent antimicrobial activity of IL-22 [134,163] ... | ||
| Interleukin 23 receptor (IL-12 receptor family) |
|
This is one of the subunits of the functional IL-23 receptor heterodimer. | ||
| Interleukin 27 receptor, alpha (IL-6 receptor family) |
|
This is the ligand binding subunit of the IL-27 receptor heterodimer, a complex with IL6ST (signal transducing subunit). | ||
| Interleukin-2 receptor subunit α (IL-2 receptor family) |
|
IL2RA is a ligand binding component of the IL-2R complex. This subunit is the molecular target of the approved biologics daclizumab (including daclizumab beta) and basiliximab. Another anti-CD25 mAb, inolimomab, has received orphan drug designation from the EMA, for the treatment of graft-versus-host disease. Phase 3 findings for this drug and indication are reported in [509] ... | ||
| Interleukin-2 receptor subunit β (IL-2 receptor family) |
|
IL2RB is a ligand binding component of the IL-2R and is required to elevate ligand affinity. It also a component of the IL-15R. | ||
| Interleukin-2 receptor subunit γ (IL-2 receptor family) |
|
IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, namely the IL-2 receptor heterotrimer, the IL-4 receptor type I, the IL-7 receptor, the IL-9 receptor, the IL-15 receptor and the IL-21 receptor. | ||
| Interleukin-31 receptor, α subunit (IL-6 receptor family) |
|
|||
| Interleukin 3 receptor, α subunit (IL-3 receptor family) |
|
This is the ligand binding subunit of the functional IL-3 receptor complex. Anti-IL-3RA monoclonal antibodies (mAbs) are being investigated for the treatment of IL-3RA (CD123) positive hematological malignancies [21,283] ... |
||
| Interleukin-4 receptor subunit α (IL-2 receptor family) |
|
IL4R is the common ligand binding subunit shared by the IL-4 receptors type I (receptor for IL-4) and type II (receptor for IL-4 and IL-13). A gain-of-function mutation in IL4R has been associated with atopy, enhanced B cell isotype switching from mu to epsilon and therefore elevated IgE levels [222] ... | ||
| Interleukin 5 receptor, α subunit (IL-3 receptor family) |
|
This is the ligand binding subunit of the functional IL-5 receptor complex. | ||
| Interleukin-6 receptor, α subunit (IL-6 receptor family) |
|
IL6R polymorphisms are associated with asthma risk [164] ... | ||
| Interleukin-6 receptor, β subunit (IL-6 receptor family) |
|
This is the common signal transducing subunit shared by members of the IL-6 family of cytokine receptors [472] ... | ||
| Interleukin-7 receptor subunit α (IL-2 receptor family) |
|
This is the ligand binding subunit of the functional IL-7 receptor complex. Effimmune are developing anti-IL7Rα monoclonal antibodies (e.g. OSE-127 [444] ... |
||
| Interleukin 9 receptor (IL-2 receptor family) |
|
The functional IL-9 receptor is a heterodimer of the ligand binding IL-9 receptor subunit and the interleukin 2 receptor γ (IL2RG) subunit. IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, including those for interleukin-2, -4, -7, and -15. ... | ||
| KIT proto-oncogene, receptor tyrosine kinase (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
|
Stem cell factor (SCF) and its receptor KIT (c-KIT) play an essential part in mast cell biology. In addition to CSF/KIT-mediated regulation of mast cell development, proliferation and survival, KIT is also reported to be involved in the adhesion of mast cells to human airway epithelial cells (a homing and adhesion role), suggesting a mechanism that could be targeted for anti-asthmatic potential [194] ... | ||
| macrophage stimulating 1 receptor (Type X RTKs: HGF (hepatocyte growth factor) receptor family) |
|
The role of RON in immuno-oncology is reviewed in [3] ... | ||
| MER proto-oncogene, tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
|
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [41,576] ... | ||
| NLRC3 (NOD-like receptor family) |
|
NLRC3 is an intracellular pattern recognition receptor of the innate immune system. It has been shown to directly interact with and inhibit the type I interferon response of the intracellular DNA sensor STING to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA viruses [349,632] ... | ||
| NLRC4 (NOD-like receptor family) |
|
As part of the innate inflammatory response to invading mobile bacteria, NLRC4 (Ipaf) in macrophages induces a pro-inflammatory response upon detection of cytosolic bacterial flagellin. In contrast, extracellular bacterial flagellin is detected by TLR5 [368] ... | ||
| NLRC5 (NOD-like receptor family) |
|
NLRC5 is an intracellular pattern recognition receptor mediating an innate immune response to viral infection [392] ... | ||
| NLRP1 (NOD-like receptor family) |
|
NLRP1 is a cytosolic sensor of bacterial infection and regulator of the resulting innate immune response [91] ... | ||
| NLRP10 (NOD-like receptor family) |
|
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [242] ... | ||
| NLRP3 (NOD-like receptor family) |
|
NLRP3 is a component of the NLRP3 inflammasome, a protein complex which activates caspase-1, and plays an important role in the regulation of inflammation and apoptosis (pyroptosis). Drug-like NLRP3 inhibitors are under investigation as novel therapeutics for the treatment of autoinflammatory diseases and neuroinflammation, as an alternative to anti-IL-1 therapies such as |
||
| NLRP6 (NOD-like receptor family) |
|
NLRP6 is an intracellular pattern recognition receptor (PRR). It is a member of the NACHT, LRR and PYD domains-containing protein (NALP) subfamily of PRRs. The presence of NALPs in inflammasomes underlies their involvement in regulating proinflammatory caspases (esp. caspase 1) ... | ||
| NLRP7 (NOD-like receptor family) |
|
NLRP7 is an intracellular pattern recognition receptor (PRR). It is a member of the NACHT, LRR and PYD domains-containing protein (NALP) subfamily of PRRs. The presence of NALPs in inflammasomes underlies their involvement in regulating proinflammatory caspases (esp. caspase 1) ... | ||
| NLRX1 (NOD-like receptor family) |
|
NLRX1 is an intracellular pattern recognition receptor that plays a role in host immunity to certain bacterial infections. | ||
| nucleotide binding oligomerization domain containing 1 (NOD-like receptor family) |
|
NOD1 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing a D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety. Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activ ... |
||
| nucleotide binding oligomerization domain containing 2 (NOD-like receptor family) |
|
NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP). Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activity; NF-κB being a major ... |
||
| Oncostatin M-specific receptor, β subunit (IL-6 receptor family) |
|
Oncostatin M-specific receptor, β subunit (OSMR) is a component of two functional heterodimeric receptor complexes: 1. OSMR+ interleukin-6 receptor, β subunit (IL6ST) forms the receptor for oncostatin M 2. OSMR+ interleukin-31 receptor, α subunit forms the recept ... |
||
| OX40 (Tumour necrosis factor (TNF) receptor family) |
|
The OX40/OX40L pair is involved in late T-cell costimulatory signalling and both are transiently expressed following antigen recognition. Blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [590] ... | ||
| receptor activator of NF-kappa B (Tumour necrosis factor (TNF) receptor family) |
|
RANK is the receptor for RANK-ligand (RANKL). It is associated with immune cell function and lymph node development, in addition to bone remodeling and repair, thermal regulation, and mammary gland development. Signals to NF-κB and JNK via TRAF adaptor proteins. | ||
| RTP Type C (Receptor tyrosine phosphatase (RTP) family) |
|
CD45 is a high molecular weight cell surface glycoprotein expressed by cells of hematopoietic origin. Alternate transcripts lead to expression of isoforms that differ in their extracellular (ligand binding) domain (potentially facilitating differential and/or cell type specific biological functions [131] ... | ||
| single Ig and TIR domain containing (Immunoglobulin-like family of IL-1 receptors) |
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IL-1R8 has been identified as a natural killer (NK) cell checkpoint that is involved in regulating NK cells' anti-viral and anti-tumour effector functions [373] ... | ||
| TLR1 (Toll-like receptor family) |
|
TLR1/2 heterodimers detect and respond to bacterial triacyl lipopeptides [559] ... | ||
| TLR10 (Toll-like receptor family) |
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To date, ligands and biological functions of human TLR10 remain unclear. However, evidence suggests it plays a modulatory role with predominantly inhibitory (anti-inflammatory) effects [417] ... | ||
| TLR2 (Toll-like receptor family) |
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TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [387] ... | ||
| TLR3 (Toll-like receptor family) |
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TLR3 is an endosomal anti-viral receptor [559] ... | ||
| TLR4 (Toll-like receptor family) |
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TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [53,445] ... | ||
| TLR5 (Toll-like receptor family) |
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TLR5 induces a pro-inflammatory response upon detection of extracellular bacterial flagellin from invading mobile bacteria [368] ... | ||
| TLR6 (Toll-like receptor family) |
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TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides (LP) from bacterial cell membranes, and effect an immune response [160] ... | ||
| TLR7 (Toll-like receptor family) |
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TLR7 is an endosomal receptor detecting ssRNA [559] ... | ||
| TLR8 (Toll-like receptor family) |
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TLR8 is an endosomal receptor detecting ssRNA [559] ... | ||
| TLR9 (Toll-like receptor family) |
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TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [559] ... | ||
| tumor necrosis factor receptor 1 (Tumour necrosis factor (TNF) receptor family) |
|
We have included TNFR1 in GtoImmuPdb based on it being a receptor for lymphotoxin-α, a cytotoxic protein performing a variety of important roles in immune system development and regulation [198,397] ... | ||
| tumor necrosis factor receptor 2 (Tumour necrosis factor (TNF) receptor family) |
|
TNFR2 is a receptor for lymphotoxin-α, and the membrane form of tumour necrosis factor (TNF). It plays a variety of important roles in immune system development and regulation [198,397] ... | ||
| Transporters | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| L-type amino acid transporter 1 (SLC7 family) |
|
LAT1 has been identified as being a key transporter of the essential amino acids [216] ... | ||
| NRAMP1 (SLC11 family of proton-coupled metal ion transporters) |
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NRAMP1 / SLC11A1 appears to be involved in macrophage antimicrobial action against intracellular pathogens, and although its precise mechanism is not fully resolved, evidence indicates its involvement in the activation of phagocytes and synthesis of proinflammatory cytokines. Polymorphisms in the human SLC11A1 gene have been associated with susceptibility to several infections [63,513,516] ... | ||
| Peptide transporter 3 (SLC15 family of peptide transporters) |
|
SLC15A3 and SLC15A4 are preferentially expressed by cells within the lymphatic system, including dendritic cells. Expression of these two genes is upregulated in response to TLR stimulation [386,514] ... | ||
| Peptide transporter 4 (SLC15 family of peptide transporters) |
|
SLC15A4 is an oligopeptide transporter that is expressed in early endosomes, and which is involved in NOD1-dependent NF-κB signaling [300] ... | ||
| Other Protein Targets | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| absent in melanoma 2 (Absent in melanoma (AIM)-like receptors (ALRs)) |
|
AIM2 primarily senses cytosolic DNA and initiates formation of an inflammasome to drive IL-1β cleavage and secretion. | ||
| advanced glycosylation end-product specific receptor (Immunoglobulin like domain containing proteins) |
|
RAGE is a single chain, membrane bound immunoglobulin type protein [391,485,609] ... | ||
| B7-H3 (CD276) (Other immune checkpoint proteins, CD molecules) |
|
B7-H3 is an immunoregulatory receptor involved in T cell activation and IFN-γ production [98,148] ... | ||
| baculoviral IAP repeat containing 2 (Inhibitors of apoptosis (IAP) protein family) |
|
Cellular inhibitors of apoptosis proteins BIRC2 and BIRC3 are required for efficient caspase-1 activation by the inflammasome [290] ... | ||
| baculoviral IAP repeat containing 3 (Inhibitors of apoptosis (IAP) protein family) |
|
Cellular inhibitor of apoptosis proteins (cIAPs) suppress apoptosis thereby promoting cell survival, and participate in the immune response (e.g. negative regulation of the necrosome, inflammasome and ripoptosome. In asthma, cIAPs extend the survival of neutrophils, macrophages and eosinophils, prolonging the inflammation. The minor alleles of single nucleotide polymorphisms in BIRC3 are shown to correlate with reduced numbers of circulating eosinophils and neutrophils, suggesting a protective effect against the development of asthma[471] ... | ||
| BCL2 apoptosis regulator (B-cell lymphoma 2 (Bcl-2) protein family) |
|
The role of Bcl-2 family members in immunity and disease is reviewed in [149] ... | ||
| Bcl-2-like 1 (B-cell lymphoma 2 (Bcl-2) protein family) |
|
The role of Bcl-2 family members in immunity and disease is reviewed in [5] ... | ||
| BCL6 transcription repressor (BTB (POZ) domain containing TFs) |
|
BCL6/corepressor complexes are important for the formation of germinal centers and differentiation and proliferation of lymphocytes. Oncogenic mutations in BCL6 lead to the development of diffuse large B-cell lymphoma cells from germinal center B cells. Disruption of BCL6/corepressor complex formation by pharmacological inhibitors has therefore been identified as a novel drug mechanism with potential for the treatment of autoimmune diseases and cancer [81,88] ... | ||
| butyrophilin like 3 (Butyrophilin and butyrophilin-like proteins) |
|
BTNL3 and BTNL8 are two proteins expressed on the surface of human gut epithelial cells that are involved in shaping the constitution of gut resident dendritic γδ T cells [144] ... | ||
| butyrophilin like 8 (Butyrophilin and butyrophilin-like proteins) |
|
BTNL3 and BTNL8 are two proteins expressed on the surface of human gut epithelial cells that are involved in shaping the constitution of gut resident dendritic γδ T cells [144] ... | ||
| butyrophilin subfamily 3 member A1 (Butyrophilin and butyrophilin-like proteins) |
|
Vγ2Vδ2 (a.k.a. Vγ9Vδ2) T cells bridge the gap between innate and adaptive immunity and play roles in microbial immunity and tumour immunity [376] ... | ||
| CD14 molecule (CD molecules) |
|
Because of its key role in amplifying the immune response, CD14 is being targeted for pharmacological modulation. Implicit Bioscience have a first-in-class anti-CD14 monoclonal antbody clinical lead, IC14 [519,568] ... | ||
| CD2 (CD molecules) |
|
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [610] ... | ||
| CD24 molecule (CD molecules) |
|
CD24 is a small GPI-anchored sialoglycoprotein that is expressed by immune cells. It is involved in B cell and T cell functions. CD24 binds to SIGLEC10 in an interaction that selectively suppresses the immune response to danger-associated molecular patterns (DAMPs). This latter action is being explo ... | ||
| CD28 (Other immune checkpoint proteins, CD molecules) |
|
CD28 is expressed on the surface of T cells and is required for the co-stimulatory signal essential for the activation, proliferation and survival of T cells, and Th2 cell development. CD28 acts in concert with the T cell receptor to stimulate cytokine release (promotes IL-2 production). CD28 binds the the B7 proteins CD80 and CD86 on the surface of antigen presenting cells to effect a co-stimulatory signal to T cells. In contrast, CTLA-4 delivers a co-inhibitory signal via CD80/CD86 [11] ... | ||
| CD33 (Other immune checkpoint proteins, Sialic acid binding Ig like lectins, CD molecules) |
|
CD33 (SIGLEC3) is a myeloid cell I-type (Ig-type) lectin that binds glycans containing sialic acids [182] ... | ||
| CD36 molecule (CD molecules) |
|
CD36 expressed by macrophages plays a key role in the recognition and phagocytosis (scavenging) of multiple ligands that are recognised either as damage-associated molecular patterns (DAMPs) released by apoptotic cells, or as potentially dangerous pathogen-associated ligands. CD36 associates with specific Toll-like receptor (TLR) DAMP-detecting heterodimers when bound by certain ligands, and following internalisation of the ligand/CD36/TLR clusters, inflammatory responses (e.g. NF-κB-dependent production of CXCL1, CXCL2, CCL9 and CCL5, NLRP3 inflammasome-mediated IL-1B production, and NF-κB-dependent production of TNF in reponse to microbial diacylated lipopeptide) are triggered. Pharmacological modulation of CD36/TLR signalling is being explored as a strategy to suppress macrophage-driven inflammation [133,555,631] ... | ||
| CD38 (CD molecules, Abscisic acid receptor complex) |
|
CD38 is a type II transmembrane glycoprotein, that is widely expressed on immune cells and is involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [202] ... | ||
| CD3e (CD molecules) |
|
CD3e is a subunit of the T cell receptor (TCR)-CD3 complex that mediates T cell receptor signal transduction in response to antigen detection. The TCR complex contains a CD3γ chain (CD3G), a CD3δ chain (CD3D), and two CD3ε chains (CD3E), plus the TCR (that can be α/β, or γ/δ type in the subsets of T cells named after the TCR they express) and the ζ-chain (zeta-chain). CD3e plays a crucial role in T cell development, highlighted by the discovery that defects in CD3e cause severe immunodeficiency [135,517] ... |
||
| CD4 (CD molecules) |
|
CD4 is being targeted for clinical utility in inflammatory diseases like rheumatoid arthritis (RA), neoplasms derived from T helper cells (T cell lymphomas and related malignancies), and for anti-HIV potential. Depending on the design of CD4 targeting antibodies, they can produce immunosuppressive effects via activation of Tregs and induction of tolerance, block HIV binding to CD4 to prevent HIV infection, or induce depletion of CD4+ T cells by apoptosis, ADCC, or CDC [280,570] ... | ||
| CD47 (CD molecules) |
|
CD47 belongs to the immunoglobulin superfamily and is reported to bind membrane integrins and the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). It is a ubiquitously expressed membrane protein that is a 'marker of self', and which is involved in self tolerance. Binding to SIRPα produces an anti-phagocytic signal. CD47 expression is hijacked by cancer cells to evade immune surveillance and macrophage-mediated removal. Anti-CD47 monoclonal antibodies are being investigated as novel immuno-oncology agents [330] ... | ||
| CD6 (CD molecules) |
|
CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes and associated with autoimmune responses. CD6 interacts with activated leucocyte-cell adhesion molecule (ALCAM/CD166), found on antigen presenting cells. This interaction induces the production of proinflammatory cytokines [383] ... | ||
| CD74 (CD molecules) |
|
CD74 is a type II transmembrane glycoprotein which associates with the MHC class II α and β chains and directs the transport of class II molecules to lysosomal and endosomal compartments [117] ... | ||
| CD80 (Other immune checkpoint proteins, CD molecules) |
|
CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t ... | ||
| CD86 (Other immune checkpoint proteins, CD molecules) |
|
CD86 (B7-2) is a type I membrane immunoglobulin. It is expressed on antigen-presenting cells and in association with CD80 provides the costimulatory signal necessary for T cell activation and survival. CD86 interacts with CD28 or CTLA-4 on T cells. It is the interaction with CTLA-4 that is targeted ... | ||
| chitinase 3 like 1 (Chitinase-like proteins) |
|
CHI3L1 is recognised as a proinflammatory mediator in the development and progression of Th2 inflammation, such as in allergic reactions [76] ... | ||
| claudin 18 (Claudins) |
|
Claudin-18.1 is expressed exclusively in the tight junctions of lung epithelia. Claudin-18 deficiency has been identified as a contributor to airway epithelial barrier dysfunction and asthmatic reactions to air-borne antigens [532] ... | ||
| C-type lectin domain family 4 member A (C-type lectin-like receptors (CLRs)) |
|
CLEC4A is an pattern recognition receptor and immunoreceptor that functions in cell adhesion, cell-cell signalling, glycoprotein turnover, and plays roles in inflammation and the immune response. It contains a immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain. | ||
| C-type lectin domain family 4 member E (C-type lectin-like receptors (CLRs)) |
|
Mincle is an FcRγ-associated membrane receptor involved in initiating the innate immune response upon recognition of endogenous and exogenous ligands including Sin3A-associated protein (SAP130), α-mannan on fungal cell walls and mycobacterial cord factor (trehalose-6,6′-dimycolate (TDM)) [67] ... | ||
| C-type lectin domain family 6 member A (C-type lectin-like receptors (CLRs)) |
|
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