Abstract
TIR8, also known as single Ig IL-1-related receptor, is a member of the IL-1 receptor/Toll-like receptor (TLR) superfamily, which acts as an intracellular decoy for components of the signaling pathway. Here we report that Tir8 has a unique pattern of expression, which includes mucosal tissues and dendritic cells (DC). Tir8-deficient DC showed increased cytokine production in response to TLR agonists (lipopolysaccharide, CpG oligodeoxynucleotides). Tir8-deficient mice had normal susceptibility to systemic lipopolysaccharide toxicity and to i.p. or s.c. inflammation. However, Tir8-deficient mice were more susceptible to intestinal inflammation. Thus, TIR8 represents a negative pathway of regulation of the IL-1 receptor/TLR system, expressed in epithelial cells and DC, crucial for tuning inflammation in the gastrointestinal tract.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chemokines / biosynthesis
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Chemokines / genetics
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Cytokines / biosynthesis
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Cytokines / genetics
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Dendritic Cells / immunology
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Enteritis / etiology*
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Enteritis / genetics
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Enteritis / immunology
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Enteritis / pathology
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Intestinal Mucosa / immunology
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Lipopolysaccharides / toxicity
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Cell Surface / deficiency
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Receptors, Cell Surface / genetics
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Receptors, Interleukin-1 / deficiency*
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Receptors, Interleukin-1 / genetics
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Toll-Like Receptors
Substances
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Chemokines
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Cytokines
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Lipopolysaccharides
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Membrane Glycoproteins
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Interleukin-1
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Tir8 protein, mouse
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Toll-Like Receptors