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

2004; National Academy of Sciences; Volume: 101; Issue: 10 Linguagem: Inglês

10.1073/pnas.0308680101

1091-6490

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

Cytokine Signaling Pathways and Interactions

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.