CCR8 | Chemokine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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CCR8

target has curated data in GtoImmuPdb

Target id: 65

Nomenclature: CCR8

Family: Chemokine receptors

Contents:

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 355 3p22 CCR8 C-C motif chemokine receptor 8 12,14-15,17-18
Mouse 7 353 9 F4 Ccr8 chemokine (C-C motif) receptor 8 7
Rat 7 - 8q32 Ccr8 C-C motif chemokine receptor 8
Previous and Unofficial Names
ChemR1 [15] | CKR-L1 [18] | TER1 [11-12] | GPR-CY6
Database Links
Specialist databases
GPCRDB ccr8_human (Hs), ccr8_mouse (Mm)
Other databases
ChEMBL Target CHEMBL4596 (Hs), CHEMBL1075278 (Mm)
Ensembl Gene ENSG00000179934 (Hs), ENSMUSG00000042262 (Mm), ENSRNOG00000026759 (Rn)
Entrez Gene 1237 (Hs), 12776 (Mm), 301066 (Rn)
Human Protein Atlas ENSG00000179934 (Hs)
KEGG Gene hsa:1237 (Hs), mmu:12776 (Mm), rno:301066 (Rn)
OMIM 601834 (Hs)
Pharos P51685 (Hs)
RefSeq Nucleotide NM_005201 (Hs), NM_007720 (Mm), XM_236704 (Rn)
RefSeq Protein NP_005192 (Hs), NP_031746 (Mm), XP_236704 (Rn)
UniProtKB P51685 (Hs), P56484 (Mm)
Wikipedia CCR8 (Hs)
Natural/Endogenous Ligands
CCL1 {Sp: Human} , CCL1 {Sp: Mouse}
CCL8 {Sp: Mouse}
Comments: CCL1 is the principal endogenous agonist

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]CCL1 (human) Hs Full agonist 8.9 – 9.7 pKd 10,14
⤷ pKd 8.9 – 9.7 (Kd 1.2x10-9 – 2.13x10-10 M) [10,14]
[125I]CCL1 (mouse) Mm Full agonist 8.7 pKd 7
⤷ pKd 8.7 [7]
vMIP-I Hs Full agonist 8.9 – 9.9 pIC50 5,10
⤷ pIC50 8.9 – 9.9 [5,10]
CCL1 {Sp: Human} Hs Full agonist 8.5 – 9.8 pIC50 5,8,10
⤷ pIC50 8.5 – 9.8 [5,8,10]
ZK 756326 Hs Full agonist 5.7 pIC50 8
⤷ pIC50 5.7 [8]
CCL8 {Sp: Mouse} Hs Agonist - -
⤷
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
vMCC-I Hs Antagonist 9.4 pIC50 5
⤷ pIC50 9.4 (IC50 3.9x10-10 M) [5]
viral macrophage inflammatory protein-II Hs Antagonist 8.1 pIC50 5
⤷ pIC50 8.1 [5]
Immunopharmacology Comments
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.
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0004950 chemokine receptor activity TAS
GO:0016493 C-C chemokine receptor activity IBA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes
GO:0004950 chemokine receptor activity TAS
GO:0016493 C-C chemokine receptor activity IBA
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Calcium channel
References:  17
Tissue Distribution
Glomerular podocytes.
Species:  Human
Technique:  RT-PCR.
References:  9
Monocytes.
Species:  Mouse
Technique:  RT-PCR.
References:  13
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of MAP kinase cascade activity in murine BW5147 cells endogenously expressing the CCR8 receptor.
Species:  Mouse
Tissue:  BW5147 cells.
Response measured:  ERK2 activation.
References:  16
Measurement of Ca2+ levels in the murine pre-B cell line, 300-19, transfected with the human CCR8 receptor.
Species:  Human
Tissue:  murine 300-19 cells.
Response measured:  Ca2+ mobilisation.
References:  14
Measurement of chemotaxis of the murine pre-B cell line, 300-19, transfected with the human CCR8 receptor.
Species:  Human
Tissue:  murine 300-19 cells.
Response measured:  Chemotaxis.
References:  14
Detection of HIV-1 infection of NP-2 cells expressing CD4 and transfected with the human CCR8 receptor.
Species:  Human
Tissue:  NP-2/CD4 cells.
Response measured:  HIV-1 infection.
References:  11
Measurement of Ca2+ levels in HEK 293 cells transfected with the mouse CCR8 receptor.
Species:  Mouse
Tissue:  HEK 293 cells.
Response measured:  Ca2+ mobilisation.
References:  8
Measurement of chemotaxis of Jurkat cells transfected with the human CCR8 receptor.
Species:  Human
Tissue:  Jurkat cells.
Response measured:  Chemotaxis.
References:  1
Differentiation of human umbilical vein endothelial cells (HUVECs) into capillary-like structures.
Species:  Human
Tissue:  HUVECs
Response measured:  Angiogenesis.
References:  2
Physiological Functions
Eosinophil recruitment to the lung.
Species:  Mouse
Tissue:  In vivo.
References:  3
Migration of dendritic cells from the skin to the lymph nodes.
Species:  Mouse
Tissue:  In vivo.
References:  13
Antiapoptotic signalling.
Species:  Mouse
Tissue:  Thymocytes.
References:  16
Physiological Consequences of Altering Gene Expression
CCR8 receptor knockout mice have reduced monocyte migration to the lymph nodes.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  13
CCR8 receptor knockout mice infected with Schistosoma mansoni soluble egg antigen, ovalbumin or cockroach antigen exhibit impaired Th2 cytokine production.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  4
CCR8 receptor knockout mice exhibit challenged with Schistosoma mansoni egg exhibit impaired Il-10 production and defective recruitment of granuloma eosinophils.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  6
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ccr8tm1Lira Ccr8tm1Lira/Ccr8tm1Lira
involves: 129S/SvEv * C57BL/6		 MGI:1201402  MP:0004800 decreased susceptibility to experimental autoimmune encephalomyelitis PMID: 12471141 
Ccr8tm1Vnk Ccr8tm1Vnk/Ccr8tm1Vnk
involves: 129P2/OlaHsd * C57BL/6		 MGI:1201402  MP:0002169 no abnormal phenotype detected PMID: 12496446 
Ccr8tm1Gma Ccr8tm1Gma/Ccr8tm1Gma
involves: 129X1/SvJ * C57BL/6J		 MGI:1201402  MP:0002169 no abnormal phenotype detected PMID: 12574386 

References

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1. Bernardini G, Hedrick J, Sozzani S, Luini W, Spinetti G, Weiss M, Menon S, Zlotnik A, Mantovani A, Santoni A et al.. (1998) Identification of the CC chemokines TARC and macrophage inflammatory protein-1 beta as novel functional ligands for the CCR8 receptor. Eur. J. Immunol., 28 (2): 582-8. [PMID:9521068]

2. Bernardini G, Spinetti G, Ribatti D, Camarda G, Morbidelli L, Ziche M, Santoni A, Capogrossi MC, Napolitano M. (2000) I-309 binds to and activates endothelial cell functions and acts as an angiogenic molecule in vivo. Blood, 96 (13): 4039-45. [PMID:11110671]

3. Bishop B, Lloyd CM. (2003) CC chemokine ligand 1 promotes recruitment of eosinophils but not Th2 cells during the development of allergic airways disease. J. Immunol., 170 (9): 4810-7. [PMID:12707363]

4. Chensue SW, Lukacs NW, Yang TY, Shang X, Frait KA, Kunkel SL, Kung T, Wiekowski MT, Hedrick JA, Cook DN et al.. (2001) Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice. J. Exp. Med., 193 (5): 573-84. [PMID:11238588]

5. Dairaghi DJ, Fan RA, McMaster BE, Hanley MR, Schall TJ. (1999) HHV8-encoded vMIP-I selectively engages chemokine receptor CCR8. Agonist and antagonist profiles of viral chemokines. J. Biol. Chem., 274 (31): 21569-74. [PMID:10419462]

6. Freeman CM, Chiu BC, Stolberg VR, Hu J, Zeibecoglou K, Lukacs NW, Lira SA, Kunkel SL, Chensue SW. (2005) CCR8 is expressed by antigen-elicited, IL-10-producing CD4+CD25+ T cells, which regulate Th2-mediated granuloma formation in mice. J. Immunol., 174 (4): 1962-70. [PMID:15699124]

7. Goya I, Gutiérrez J, Varona R, Kremer L, Zaballos A, Márquez G. (1998) Identification of CCR8 as the specific receptor for the human beta-chemokine I-309: cloning and molecular characterization of murine CCR8 as the receptor for TCA-3. J. Immunol., 160 (4): 1975-81. [PMID:9469461]

8. Haskell CA, Horuk R, Liang M, Rosser M, Dunning L, Islam I, Kremer L, Gutiérrez J, Marquez G, Martinez-A C et al.. (2006) Identification and characterization of a potent, selective nonpeptide agonist of the CC chemokine receptor CCR8. Mol. Pharmacol., 69 (1): 309-16. [PMID:16221874]

9. Huber TB, Reinhardt HC, Exner M, Burger JA, Kerjaschki D, Saleem MA, Pavenstädt H. (2002) Expression of functional CCR and CXCR chemokine receptors in podocytes. J. Immunol., 168 (12): 6244-52. [PMID:12055238]

10. Inngjerdingen M, Damaj B, Maghazachi AA. (2001) Expression and regulation of chemokine receptors in human natural killer cells. Blood, 97 (2): 367-75. [PMID:11154210]

11. Jinno A, Shimizu N, Soda Y, Haraguchi Y, Kitamura T, Hoshino H. (1998) Identification of the chemokine receptor TER1/CCR8 expressed in brain-derived cells and T cells as a new coreceptor for HIV-1 infection. Biochem. Biophys. Res. Commun., 243 (2): 497-502. [PMID:9480837]

12. Napolitano M, Zingoni A, Bernardini G, Spinetti G, Nista A, Storlazzi CT, Rocchi M, Santoni A. (1996) Molecular cloning of TER1, a chemokine receptor-like gene expressed by lymphoid tissues. J Immunol, 157: 2759-2763. [PMID:8816377]

13. Qu C, Edwards EW, Tacke F, Angeli V, Llodrá J, Sanchez-Schmitz G, Garin A, Haque NS, Peters W, van Rooijen N et al.. (2004) Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes. J. Exp. Med., 200 (10): 1231-41. [PMID:15534368]

14. Roos RS, Loetscher M, Legler DF, Clark-Lewis I, Baggiolini M, Moser B. (1997) Identification of CCR8, the receptor for the human CC chemokine I-309. J. Biol. Chem., 272 (28): 17251-4. [PMID:9211859]

15. Samson M, Stordeur P, Labbé O, Soularue P, Vassart G, Parmentier M. (1996) Molecular cloning and chromosomal mapping of a novel human gene, ChemR1, expressed in T lymphocytes and polymorphonuclear cells and encoding a putative chemokine receptor. Eur. J. Immunol., 26 (12): 3021-8. [PMID:8977299]

16. Spinetti G, Bernardini G, Camarda G, Mangoni A, Santoni A, Capogrossi MC, Napolitano M. (2003) The chemokine receptor CCR8 mediates rescue from dexamethasone-induced apoptosis via an ERK-dependent pathway. J Leukoc Biol, 73: 201-207. [PMID:12525579]

17. Tiffany HL, Lautens LL, Gao JL, Pease J, Locati M, Combadiere C, Modi W, Bonner TI, Murphy PM. (1997) Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309. J. Exp. Med., 186 (1): 165-70. [PMID:9207005]

18. Zaballos A, Varona R, Gutierrez J, Lind P, Marquez G. (1996) Molecular cloning and RNA expression of two new human chemokine receptor-like genes. Biochem Biophys Res Commun, 227: 846-853. [PMID:8886020]

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