VSIG4

Official Full Name

V-set and immunoglobulin domain containing 4

Organism

Homo sapiens

Gene ID

11326

Background

This gene encodes a v-set and immunoglobulin-domain containing protein that is structurally related to the B7 family of immune regulatory proteins. The encoded protein may be a negative regulator of T-cell responses. This protein is also a receptor for the complement component 3 fragments C3b and iC3b. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

Synonyms

CRIg; Z39IG

Cat.No.	Product Name	Price
CSC-DC017342	Panoply™ Human VSIG4 Knockdown Stable Cell Line	Inquiry
CSC-SC017342	Panoply™ Human VSIG4 Over-expressing Stable Cell Line	Inquiry
CLOE-0658	Human VSIG4(Fc) HEK293 Cell Lysate	Inquiry
CLOE-0663	Human VSIG4(His) HEK293 Cell Lysate	Inquiry
CLOE-2848	Mouse Vsig4 (Fc) HEK293 Cell Lysate	Inquiry
CLOE-2850	Mouse Vsig4 (His) HEK293 Cell Lysate	Inquiry

Cat.No.	Product Name	Price
AD17610Z	Human VSIG4 adenoviral particles	Inquiry
LV29688L	human VSIG4 (NM_001100431) lentivirus particles	Inquiry
LV29689L	human VSIG4 (NM_001184830) lentivirus particles	Inquiry
LV29690L	human VSIG4 (NM_001184831) lentivirus particles	Inquiry
LV29691L	human VSIG4 (NM_007268) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHL128686	shRNA set against Mouse Vsig4(NM_177789.4)	Inquiry
SHH445236	shRNA set against Human VSIG4 (NM_007268.2)	Inquiry
SHH445240	shRNA set against Mouse VSIG4 (NM_177789.4)	Inquiry
SHH445244	shRNA set against Rat VSIG4 (NM_001025004.1)	Inquiry
SHL128754	shRNA set against Human VSIG4(NM_007268.2)	Inquiry

Cat.No.	Product Name	Price
CDCB160020	Human VSIG4 ORF clone (BC010525)	Inquiry
CDCH100346	human VSIG4 ORF clone (NM_001184831.1)	Inquiry
CDCS407521	Human VSIG4 ORF Clone (BC010525)	Inquiry
CDFH021156	Human VSIG4 cDNA Clone(NM_001100431.1)	Inquiry
CDFH021157	Human VSIG4 cDNA Clone(NM_001184830.1)	Inquiry
CDFH021158	Human VSIG4 cDNA Clone(NM_001184831.1)	Inquiry
CDFR003781	Rat Vsig4 cDNA Clone(NM_001025004.1)	Inquiry
MiUTR1H-11171	VSIG4 miRNA 3'UTR clone	Inquiry
MiUTR1M-12719	VSIG4 miRNA 3'UTR clone	Inquiry
MiUTR1R-03165	VSIG4 miRNA 3'UTR clone	Inquiry
MiUTR3H-02705	VSIG4 miRNA 3'UTR clone	Inquiry
CDCB194491	Rabbit VSIG4 ORF clone (XM_008272723.1)	Inquiry
CDCH100344	human VSIG4 ORF clone (NM_001100431.1)	Inquiry
CDCH100348	human VSIG4 ORF clone (NM_001184830.1)	Inquiry
CDCR274371	Mouse Vsig4 ORF Clone(NM_177789.4)	Inquiry
CDCR370805	Rat Vsig4 ORF Clone(NM_001025004.1)	Inquiry

Detailed Information

The VSIG4 gene, officially named V-set and immunoglobulin domain containing 4, is located on human chromosome Xq12. It encodes a type I transmembrane protein belonging to the B7 family of immune regulatory proteins. The extracellular region of VSIG4 contains a V-set immunoglobulin-like domain and a C2-set immunoglobulin-like domain, enabling specific interactions with its ligands. VSIG4 expression is highly cell-type specific, predominantly found in tissue-resident macrophage subsets, including splenic marginal zone macrophages, peritoneal macrophages, and, under certain conditions, specific dendritic cell populations. This restricted expression pattern suggests that VSIG4 plays a crucial role in maintaining immune homeostasis within specialized tissue microenvironments. As a B7 family member, VSIG4 functions in the negative regulation of T cell–mediated immunity while simultaneously serving as a key regulator of the complement system, linking innate and adaptive immunity.

Biological Significance

VSIG4's biological significance stems from its dual role as an immunosuppressive receptor and a complement regulatory factor. In adaptive immunity, VSIG4 is a potent negative regulator of T cell activation. It interacts with as-yet incompletely defined T cell surface receptors to directly inhibit T cell proliferation and reduce the production of critical T cell growth factor IL-2. This inhibitory function is essential for preventing overactivation of T cells, maintaining peripheral immune tolerance, and facilitating the clearance of senescent or apoptotic cells in organs such as the spleen, thereby reducing the risk of autoimmune reactions.

Figure 1. Role of VSIG4 in the complement pathway and T cell activation. (Liu B, et al., 2023)

In innate immunity, VSIG4 functions as a receptor for complement fragments C3b and iC3b. By binding these fragments, VSIG4 competitively inhibits the formation and stabilization of the alternative pathway C3 convertase, preventing excessive complement activation. Overactivation of the complement system can damage host tissues, and VSIG4-mediated regulation is considered a key mechanism protecting tissues from complement-induced inflammatory injury. Particularly, VSIG4 facilitates "silent" clearance of complement-opsonized apoptotic cells, preventing unnecessary inflammation. Collectively, VSIG4 maintains immune homeostasis by suppressing T cell responses and regulating complement activation, forming a crucial barrier against excessive inflammation and tissue damage. Dysregulation of VSIG4 is associated with various autoimmune and inflammatory disorders.

Clinical Relevance

Clinically, VSIG4 is of interest as a potential immune checkpoint molecule and for its altered expression in inflammatory diseases and cancer. In autoimmune diseases, such as atypical hemolytic uremic syndrome, dysregulated alternative complement pathway activation is a key pathogenic mechanism. VSIG4, as an endogenous complement inhibitor, may influence disease susceptibility and severity, making it a significant disease-associated gene and potential therapeutic target.

In cancer immunology, VSIG4 expression on tumor-associated macrophages is thought to contribute to an immunosuppressive tumor microenvironment. By inhibiting T cell function, VSIG4 may facilitate tumor immune evasion, positioning it as a potential novel immune checkpoint similar to the PD-1/PD-L1 axis. Preclinical studies are exploring antagonistic antibodies targeting VSIG4 to block its immunosuppressive function, thereby "releasing" tumor-infiltrating T cells and enhancing antitumor immunity. Conversely, in chronic inflammation or tissue injury models, harnessing VSIG4's immunosuppressive and anti-inflammatory properties-e.g., via recombinant VSIG4 protein or agonists-may offer strategies for treating autoimmune diseases or preventing transplant rejection. Translating VSIG4 into a therapeutic target faces challenges, including the need for a precise understanding of its regulatory mechanisms in different pathological contexts, identification of its ligands, and assessment of potential systemic immune-related adverse effects.

References

Helmy KY, Katschke KJ Jr, Gorgani NN, et al. CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens. Cell. 2006;124(5):915–27.
Lee KM, Najarro DH, Yoon KJ, et al. VSIG4 is a ligand of VISTA and suppresses T cell activation. Sci Immunol. 2023;8(84):eabq1249.
Liu B, Cheng L, Gao H, et al. The biology of VSIG4: Implications for the treatment of immune-mediated inflammatory diseases and cancer. Cancer Lett. 2023 Jan 28;553:215996.

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