V-set and Ig domain-containing 4 (VSIG4) is a strong negative regulator of T cell proliferation and IL-2 production []. It also negatively regulates macrophage activation by activating the PI3K/Akt-STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/acetyl-CoA conversion, reduction in mitochondrialreactive oxygen species secretion, and macrophage inhibition [].
MS4A6A/B/C/D/E are members of the membrane-spanning 4-domains family A (MS4A), which contains at least 16 members in human. MS4A6D has been shown to interact with VSIG4 to form a surface signaling complex, which activates JAK2-STAT3-A20 cascades to inhibit NF-kB activation []. MS4A6A and MS4A6E variants have been associated with Alzheimer's disease [, , ].
