VSTM Protein Family - New B7-like Immune Checkpoint Targets

The V-set and transmembrane domain-containing protein (VSTM) family is a newly identified immunoglobulin (Ig) superfamily of transmembrane proteins. They are structurally similar to B7-like immunoregulatory proteins and consist of IgV-like and/or IgC-like extracellular domains. The VSTM family is composed of 8 proteins: VSTM1v1, VSTM1v2, VSTM2a, VSTM2b, VSTM2L, VSTM3, VSTM4 and VSTM5. Members of the VSTM family have been reported to be associated with the regulation of intrinsic functions of immune cells, adipose cells and neuronal cells. Most studies on the VSTM family have focused on their immunological function. For instance, VSTM1 and VSTM4 have been shown to play positive and negative roles in macrophage activation. VSTM3 (TIGIT, VSIG9) acts as a co-inhibitory receptor that suppresses the cytokine production of T cells and NK cells. Unlike the immune-regulating VSTM family members, VSTM2 associates with the regulation of adipogenic commitment of adipose precursors.

VSTM5 has been identified as a putative cell adhesion molecule that is expressed in the brain and promotes the formation of dendritic filopodia which are associated with neuronal morphogenesis and migration in the brain. Based on its close phylogenetic relationship with the two immune checkpoints, VISTA and TIGIT, the potential role of VSTM5 in T cell immune responses has been investigated. Consequently, VSTM5 functions as a novel immune checkpoint by regulating T cell proliferation and cytokine production, Treg generation by the maintenance of T cell energy and possibly induction of T cell apoptosis.

LIT:  VSTM5 is a novel immune checkpoint that promotes oral tolerance of cell-mediated and antibody responses: O.E. Oludada, et al.; BBRC 635, 283 (2022)

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