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
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cell Differentiation
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Evolution, Molecular
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Gene Expression Regulation / immunology
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Humans
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Inflammation
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Interleukin-1 / immunology
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Interleukin-1 / metabolism*
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Interleukin-18 / immunology
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Interleukin-18 / metabolism
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Interleukin-33
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Interleukins / immunology
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Interleukins / metabolism
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Mice
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Receptors, Interleukin-1 / genetics
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Receptors, Interleukin-1 / immunology
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Receptors, Interleukin-1 / metabolism*
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Signal Transduction / immunology
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Th1 Cells / immunology
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Th2 Cells / immunology
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Toll-Like Receptors / immunology
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Toll-Like Receptors / metabolism*
Substances
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IL33 protein, human
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Il33 protein, mouse
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Interleukin-1
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Interleukin-18
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Interleukin-33
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Interleukins
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Receptors, Interleukin-1
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TIR8 protein, human
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Tir8 protein, mouse
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Toll-Like Receptors