Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family.
Journal:
Proc. Natl. Acad. Sci. U.S.A. 2004 MarAuthors:
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
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
...[more] 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.[less]
Mesh Headings:
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