Mouse Single Ig IL1 Related Receptor (SIGIRR) Protein

Background

SIGIRR, also known as IL1R8 or TIR8, is a member of the interleukin-1 receptor (IL-1R) family but functions as a negative regulator of Toll-like receptor (TLR) and IL-1R signaling pathways. SIGIRR contains a single immunoglobulin-like domain and a Toll/interleukin-1 receptor (TIR) domain, which mediate its inhibitory activity by preventing the recruitment of adaptor proteins like MyD88 and IRAK. It dampens the activation of downstream pathways, including NF-κB, MAPK, and AP-1, which are central to pro-inflammatory cytokine production. SIGIRR is highly expressed in epithelial cells, immune cells, and tissues like the intestine, lung, and kidney, where it helps maintain immune tolerance and protect against excessive inflammation. Dysregulation or deficiency of SIGIRR is linked to chronic inflammatory diseases, including inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and autoimmune disorders, where unchecked signaling exacerbates tissue damage. Knockout studies reveal heightened inflammatory responses, increased cytokine production, and susceptibility to autoimmune and infectious diseases, emphasizing its role as a negative regulator in inflammation, immune homeostasis, and tissue protection.