TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization

Trends Immunol. 2009 Sep;30(9):439-46. doi: 10.1016/j.it.2009.06.001. Epub 2009 Aug 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Evolution, Molecular
  • Gene Expression Regulation / immunology
  • Humans
  • Inflammation
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism*
  • Interleukin-18 / immunology
  • Interleukin-18 / metabolism
  • Interleukin-33
  • Interleukins / immunology
  • Interleukins / metabolism
  • Mice
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / immunology
  • Receptors, Interleukin-1 / metabolism*
  • Signal Transduction / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism*

Substances

  • IL33 protein, human
  • Il33 protein, mouse
  • Interleukin-1
  • Interleukin-18
  • Interleukin-33
  • Interleukins
  • Receptors, Interleukin-1
  • TIR8 protein, human
  • Tir8 protein, mouse
  • Toll-Like Receptors