V-set immunoglobulin domain-containing 4 (VSIG4)

V-set immunoglobulin domain-containing 4 (VSIG4), also known as Complement Receptor of the Immunoglobulin superfamily (CRIg), is a type I transmembrane protein primarily expressed on tissue-resident macrophages, most notably Kupffer cells in the liver (UniProt Q9Y279). It serves a dual role in the immune system: acting as a complement receptor that binds C3b and iC3b to facilitate the rapid clearance of opsonized pathogens from the circulation, and functioning as a potent negative regulator of T-cell activation (He et al., 2006, PMID: 16127454). In the tumor microenvironment, VSIG4 is frequently upregulated on tumor-associated macrophages (TAMs), where it suppresses T-cell proliferation and IL-2 production, thereby contributing to immune evasion (Vogt et al., 2006, PMID: 17121957). Because of this immunosuppressive function, VSIG4 is considered a promising B7-family-related immune checkpoint target for cancer immunotherapy (NCBI Gene ID: 11326). Conversely, in autoimmune and inflammatory contexts, VSIG4-Ig fusion proteins are being explored for their ability to dampen excessive immune responses (Jung et al., 2012, PMID: 22566012). Therapeutic development currently focuses on monoclonal antibodies to block its inhibitory effects in oncology and agonists or fusion proteins to leverage its anti-inflammatory properties in diseases like rheumatoid arthritis.

Other names

Complement receptor of the immunoglobulin superfamilyCRIgZ39IGProtein Z39Ig

Binding to C3b and iC3b to facilitate clearance of opsonized particles; binding to an unidentified receptor on T-cells to inhibit TCR-mediated signaling and proliferation.