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

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.

Pubmed ID: 14993616


  • Garlanda C
  • Riva F
  • Polentarutti N
  • Buracchi C
  • Sironi M
  • De Bortoli M
  • Muzio M
  • Bergottini R
  • Scanziani E
  • Vecchi A
  • Hirsch E
  • Mantovani A


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 9, 2004

Associated Grants


Mesh Terms

  • Animals
  • Chemokines
  • Cytokines
  • Dendritic Cells
  • Enteritis
  • Intestinal Mucosa
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Interleukin-1
  • Toll-Like Receptors