The biology of VSIG4: Implications for the treatment of immune-mediated inflammatory diseases and cancer

• Published in: Cancer letters 2023-01, Vol.553, p.215996-215996, Article 215996
• Main Authors: Liu, Bei, Cheng, Li, Gao, Honghao, Zhang, Jiale, Dong, Yanxin, Gao, Wenda, Yuan, Shunzong, Gong, Taiqian, Huang, Wenrong
• Format: Article
• Language: English
• Subjects: Ablation; Amino acids; Animals; Bacteria; Biology; Biomarkers; Body fat; By products; Cancer; Cell activation; Cell differentiation; Complement activation; Complement component C3; Gram-positive bacteria; Growth factors; Hemophagocytic lymphohistiocytosis; Homeostasis; Humans; Immune checkpoint; Immune checkpoint inhibitors; Immunoglobulins; Inflammatory diseases; Kinases; Liver; Lymphocytes T; Macrophage activation syndrome; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Neoplasms - therapy; Opsonization; Pathogens; Phagocytosis; Proteins; Receptors, Complement - metabolism; Tumor necrosis factor-TNF; Tumor-associated macrophages; VSIG4
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2022.215996

V-set and immunoglobulin domain containing 4 (VSIG4), a type I transmembrane receptor exclusively expressed in a subset of tissue-resident macrophages, plays a pivotal role in clearing C3-opsonized pathogens and their byproducts from the circulation. VSIG4 maintains immune homeostasis by suppressing the activation of complement pathways or T cells and inducing regulatory T-cell differentiation, thereby inhibiting the development of immune-mediated inflammatory diseases but enhancing cancer progression. Consequently, VSIG4 exhibits a potential therapeutic effect for immune-mediated inflammatory diseases, but also is regarded as a novel target of immune checkpoint inhibition in cancer therapy. Recently, soluble VSIG4, the extracellular domain of VSIG4, shed from the surface of macrophages, has been found to be a biomarker to define macrophage activation-related diseases. This review mainly summarizes recent new findings of VSIG4 in macrophage phagocytosis and immune homeostasis, and discusses its potential diagnostic and therapeutic usage in infection, inflammation, and cancer. •Expression of VSIG4 and potential regulatory mechanisms in macrophages.•Role of VSIG4 in regulating macrophage phagocytosis.•Role of VSIG4 in complement pathway and T cell activation.•Role of VSIG4 in tumor microenvironment.•sVSIG4 in diseases related to macrophage activation and beyond.