SIGIRR, a negative regulator of Toll-like receptor - Interleukin 1 receptor signaling

David Wald, Jinzhong Qin, Zhendong Zhao, Youcun Qian, Mayumi Naramura, Liping Tian, Jennifer Towne, John E. Sims, George R. Stark, Xiaoxia Li

Research output: Contribution to journalArticlepeer-review

515 Scopus citations


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 factorkB 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.

Original languageEnglish (US)
Pages (from-to)920-927
Number of pages8
JournalNature Immunology
Issue number9
StatePublished - Sep 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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