TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization.
TIR8, also known as single Ig IL-1 receptor (IL-R)-related molecule, SIGIRR, is a member of the IL-1R like (ILR) family. Unlike most other members of this family, it has a single extracellular Ig domain, a long cytoplasmic tail and a Toll/IL-1R (TIR) domain with two amino acid substitutions possibly consistent with non-conventional signaling. The TIR8 structure and pattern of expression are conserved in evolution from birds to humans. Current evidence suggests that TIR8 inhibits signaling receptor complexes of IL-1 family members associated with Th1 (IL-18), Th2 (IL-33) and Th17 (IL-1) differentiation. TIR8 also dampens TLR-mediated activation. The ability to dampen signaling from ILR family members and TLRs makes TIR8 a key regulator of inflammation, cancer-related inflammation, and autoimmunity.
Garlanda
Cecilia
C
Istituto Clinico Humanitas, IRCCS, Department of Immunology and Inflammation, Rozzano, Milan, Italy. cecilia.garlanda@humanitas
Anders
Hans-Joachim
HJ
Mantovani
Alberto
A
D000818:Animals; D002454:Cell Differentiation; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*
D007375:Interleukin-1; D020382:Interleukin-18; D000067596:Interleukin-33; D007378:Interleukins; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; C506536:IL33 protein, human; C506535:Il33 protein, mouse; C546891:SIGIRR protein, human; C484529:SIGIRR protein, mouse