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

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

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Review

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

Cecilia Garlanda et al. Trends Immunol. 2009 Sep.

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.

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