V-set and transmembrane domain-containing protein 1 (VSTM1) (VSTM1)

V-set and transmembrane domain-containing protein 1 (VSTM1), also known as Signal inhibitory receptor on leukocytes 1 (SIRL-1), is a type I transmembrane glycoprotein primarily expressed on the surface of myeloid cells, including neutrophils and monocytes (UniProt, Q6UX27). It serves as a potent inhibitory receptor, utilizing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic domain to recruit protein tyrosine phosphatases SHP-1 and SHP-2, thereby dampening pro-inflammatory signaling pathways (Meyaard, 2008). A key biological function of VSTM1 is the negative regulation of neutrophil extracellular trap (NET) formation, a process known as NETosis, which is critical for preventing excessive tissue damage during inflammation (van Avondt et al., 2013). Dysregulation of VSTM1 expression or function has been implicated in various inflammatory diseases, such as asthma and rheumatoid arthritis, and it plays a role in the immune response to respiratory syncytial virus (RSV) (NCBI Gene, 94059). While VSTM1 is recognized as a promising therapeutic target for managing chronic inflammation and potentially as an immune checkpoint in oncology, there are currently no approved drugs targeting this molecule. Research is ongoing to develop monoclonal antibodies that can either agonize or antagonize the receptor depending on the desired therapeutic outcome (van Avondt et al., 2013).

Other names

Signal inhibitory receptor on leukocytes 1SIRL-1SIRL1UNQ3033/PRO9855

Inhibitory signaling via ITIM-mediated recruitment of SHP-1 and SHP-2 phosphatases to suppress myeloid cell activation and pro-inflammatory cytokine production.