Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family

Cecilia Garlanda, Federica Riva, Nadia Polentarutti, Chiara Buracchi, Marina Sironi, Maida De Bortoli, Marta Muzio, Raffaella Bergottini, Eugenio Scanziani, Annunciata Vecchi, Emilio Hirsch, Alberto Mantovani

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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.

Original languageEnglish
Pages (from-to)3522-3526
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number10
DOIs
Publication statusPublished - Mar 9 2004

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ASJC Scopus subject areas

  • Genetics
  • General

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