Vsig4, also known as V-set and immunoglobulin domain containing 4, is a type I transmembrane receptor. It is mainly expressed on tissue-resident and M2 macrophages and plays a pivotal role in clearing C3-opsonized pathogens and their byproducts from the circulation. It maintains immune homeostasis by suppressing the activation of complement pathways or T cells and inducing regulatory T-cell differentiation. It is also involved in multiple signaling pathways such as JAK2-STAT3-A20, which further results in nuclear factor κB suppression and Nlrp3 and Il-1β repression [2,3].

In the context of acute myocardial infarction (AMI), VSIG4 knockout and adoptive bone marrow transfer chimeric models showed that VSIG4 promotes scar formation, orchestrates the myocardial inflammatory response, and promotes TGF-β1 and IL-10. Hypoxia was found to promote VSIG4 expression in cultured bone marrow M2 macrophages, leading to the conversion of cardiac fibroblasts to myofibroblasts [1].

In experimental autoimmune encephalomyelitis (EAE) and dextran sulfate sodium (DSS)-induced colitis, Vsig4-/-mice exhibited exaggerated NLRP3 and IL-1β expression, making them more severely affected. Agonistic VSIG4 antibodies showed therapeutic efficacy in mouse EAE [3].

In glioblastoma, silencing VSIG4 inhibited tumor cell proliferation, invasion, and migration, and promoted pyroptosis, with the JAK2/STAT3 pathway being a downstream regulator [4]. In aggressive cancers like anaplastic thyroid cancer and pancreatic cancer, targeting VSIG4 + TAMs by VSIG4 deficiency or blockade limited tumor growth and metastasis [5].

In conclusion, Vsig4 is crucial for immune homeostasis and is involved in multiple disease-related processes. Gene knockout models in mice have been instrumental in revealing its role in diseases such as AMI, EAE, DSS-induced colitis, glioblastoma, and aggressive cancers, providing potential therapeutic targets for these conditions.