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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
RefSeq Nucleotide
RefSeq Protein
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)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Immuno Process:  B cell (activation)
Immuno Process:  Inflammation
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
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
References:  6
Vsir-/- mice exhibit a dramatically increased response to antigen stimulation.
Species:  Mouse
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.


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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 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY,