SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling
- PMID: 12925853
- DOI: 10.1038/ni968
SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling
Abstract
The Toll-like receptor-interleukin 1 receptor signaling (TLR-IL-1R) receptor superfamily is important in differentially recognizing pathogen products and eliciting appropriate immune responses. These receptors alter gene expression, mainly through the activation of nuclear factor-kappaB and activating protein 1. SIGIRR (single immunoglobulin IL-1R-related molecule), a member of this family that does not activate these factors, instead negatively modulates immune responses. Inflammation is enhanced in SIGIRR-deficient mice, as shown by their enhanced chemokine induction after IL-1 injection and reduced threshold for lethal endotoxin challenge. Cells from SIGIRR-deficient mice showed enhanced activation in response to either IL-1 or certain Toll ligands. Finally, biochemical analysis indicated that SIGIRR binds to the TLR-IL-1R signaling components in a ligand-dependent way. Our data show that SIGIRR functions as a biologically important modulator of TLR-IL-1R signaling.
Comment in
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SIGIRR puts the brakes on Toll-like receptors.Nat Immunol. 2003 Sep;4(9):823-4. doi: 10.1038/ni0903-823. Nat Immunol. 2003. PMID: 12942080 No abstract available.
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