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V-set immunoregulatory receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2956

Nomenclature: V-set immunoregulatory receptor

Abbreviated Name: VISTA

Family: Other immune checkpoint proteins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 311 10q22.1 VSIR V-set immunoregulatory receptor
Mouse 1 308 10 B4 Vsir V-set immunoregulatory receptor
Rat 1 309 20q11 Vsir V-set immunoregulatory receptor
Previous and Unofficial Names Click here for help
B7-H5 | B7H5 | PD-1H | programmed death-1 homologue-1 | V-domain Ig suppressor of T cell activation | VISTA
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Antibody Comments
An experimental anti-Vsir monoclonal antibody has shown preventative action in graft-versus-host disease in semi- and fully allogeneic murine models [4].
Immunopharmacology Comments
V-set immunoregulatory receptor (VSIR) is commonly referred to as VISTA in the literature corpus. This is an Ig superfamily (B7 family) protein that acts as an inhibitory immune-checkpoint molecule. In common with other T cell co-inhibitory receptors (e.g. CTLA-4, PD-1, TIM3, and LAG3) it is involved in maintaining peripheral tolerance [6] and controlling immune responses against self [8], infectious agents [1], and cancer [2,5]. Experimental pharmacological interventions that enhance VISTA regulatory activity are being explored as a novel mechanism for the treatment of autoimmune disease, as cancer immunotherapy [7], and for graft-versus-host disease [4].
Cell Type Associations
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   myeloid dendritic cell (CL:0000782)
Comment:  Constitutively expressed on CD11b+ myeloid DCs.
References:  9
Immuno Cell Type:  Other T cells
Cell Ontology Term:   naive T cell (CL:0000898)
Comment:  Expressed on naïve CD4+ and CD8+ T cells.
References:  9
Immuno Cell Type:  T cells
Cell Ontology Term:   regulatory T cell (CL:0000815)
Comment:  Expressed on Foxp3+CD4+ regulatory T cells.
References:  6
Immuno Process Associations
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 4 GO processes
GO:0002725 negative regulation of T cell cytokine production IDA
GO:0045591 positive regulation of regulatory T cell differentiation IMP
GO:2000562 negative regulation of CD4-positive, alpha-beta T cell proliferation IMP
GO:2000565 negative regulation of CD8-positive, alpha-beta T cell proliferation IMP
Immuno Process:  Immune regulation
GO Annotations:  Associated to 5 GO processes
GO:0002725 negative regulation of T cell cytokine production IDA
GO:0045591 positive regulation of regulatory T cell differentiation IMP
GO:2000562 negative regulation of CD4-positive, alpha-beta T cell proliferation IMP
GO:2000565 negative regulation of CD8-positive, alpha-beta T cell proliferation IMP
click arrow to show/hide IEA associations
GO:0050776 regulation of immune response IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0045591 positive regulation of regulatory T cell differentiation IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 5 GO processes
GO:0002725 negative regulation of T cell cytokine production IDA
GO:0032689 negative regulation of interferon-gamma production IDA
GO:0032693 negative regulation of interleukin-10 production IDA
GO:0032700 negative regulation of interleukin-17 production IDA
GO:0032720 negative regulation of tumor necrosis factor production IDA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 3 GO processes
GO:0045591 positive regulation of regulatory T cell differentiation IMP
GO:2000562 negative regulation of CD4-positive, alpha-beta T cell proliferation IMP
GO:2000565 negative regulation of CD8-positive, alpha-beta T cell proliferation IMP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0045591 positive regulation of regulatory T cell differentiation IMP
GO:2000562 negative regulation of CD4-positive, alpha-beta T cell proliferation IMP
GO:2000565 negative regulation of CD8-positive, alpha-beta T cell proliferation IMP
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0002725 negative regulation of T cell cytokine production IDA
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0002725 negative regulation of T cell cytokine production IDA
Physiological Functions Click here for help
Regulates the IL-23/IL-17 inflammatory axis.
Species:  Mouse
Tissue:  Imiquimod (IMQ)-induced murine model of psoriasis; dendritic cells, γδ T cells, Th17 T cells.
References:  6
Suppresses CD4+ and CD8+ T cell activation, to regulate both the innate and adaptive immune responses.
Species:  Mouse
Tissue: 
References:  6
Physiological Consequences of Altering Gene Expression Click here for help
Vsir-/- mice exhibit exacerbated psoriasiform inflammation in an imiquimod-induced psoriasis model.
Species:  Mouse
Tissue: 
Technique: 
References:  6
Vsir-/- mice exhibit a dramatically increased response to antigen stimulation.
Species:  Mouse
Tissue: 
Technique: 
References:  3
General Comments
This protein contains an immunoglobulin (Ig)-like domain that resembles the antibody variable domain, that has been coined the 'V-set domain'. The genes for all human V-set domain containing proteins are listed in HGNC gene group 590.

References

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1. Bharaj P, Chahar HS, Alozie OK, Rodarte L, Bansal A, Goepfert PA, Dwivedi A, Manjunath N, Shankar P. (2014) Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals. PLoS ONE, 9 (10): e109103. [PMID:25279955]

2. Böger C, Behrens HM, Krüger S, Röcken C. (2017) The novel negative checkpoint regulator VISTA is expressed in gastric carcinoma and associated with PD-L1/PD-1: A future perspective for a combined gastric cancer therapy?. Oncoimmunology, 6 (4): e1293215. [PMID:28507801]

3. Flies DB, Han X, Higuchi T, Zheng L, Sun J, Ye JJ, Chen L. (2014) Coinhibitory receptor PD-1H preferentially suppresses CD4⁺ T cell-mediated immunity. J Clin Invest, 124 (5): 1966-75. [PMID:24743150]

4. Flies DB, Wang S, Xu H, Chen L. (2011) Cutting edge: A monoclonal antibody specific for the programmed death-1 homolog prevents graft-versus-host disease in mouse models. J Immunol, 187 (4): 1537-41. [PMID:21768399]

5. Kakavand H, Jackett LA, Menzies AM, Gide TN, Carlino MS, Saw RPM, Thompson JF, Wilmott JS. (2017) Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients. Mod Pathol, 30 (12): 1666-1676. [PMID:28776578]

6. Li N, Xu W, Yuan Y, Ayithan N, Imai Y, Wu X, Miller H, Olson M, Feng Y, Huang YH et al.. (2017) Immune-checkpoint protein VISTA critically regulates the IL-23/IL-17 inflammatory axis. Sci Rep, 7 (1): 1485. [PMID:28469254]

7. Lines JL, Sempere LF, Broughton T, Wang L, Noelle R. (2014) VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy. Cancer Immunol Res, 2 (6): 510-7. [PMID:24894088]

8. Sergent PA, Plummer SF, Pettus J, Mabaera R, DeLong JK, Pechenick DA, Burns CM, Noelle RJ, Ceeraz S. (2018) Blocking the VISTA pathway enhances disease progression in (NZB × NZW) F1 female mice. Lupus, 27 (2): 210-216. [PMID:28659048]

9. Wang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, Lu LF, Gondek D, Wang Y, Fava RA et al.. (2011) VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. J Exp Med, 208 (3): 577-92. [PMID:21383057]

How to cite this page

Other immune checkpoint proteins: V-set immunoregulatory receptor. Last modified on 07/08/2019. Accessed on 03/08/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2956.