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

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 com-plement 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.

Automated summary

VSIG4 is a transmembrane receptor expressed exclusively in a subset of tissue-resident macrophages, playing a pivotal role in clearing pathogens and maintaining immune homeostasis. It has potential therapeutic effects for immune-mediated inflammatory diseases and cancer, and can serve as a biomarker for macrophage activation-related diseases.