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.
Department of Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milan, Italy.
Cecilia
C
Garlanda
Federica
F
Riva
Nadia
N
Polentarutti
Chiara
C
Buracchi
Marina
M
Sironi
Maida
M
De Bortoli
Marta
M
Muzio
Raffaella
R
Bergottini
Eugenio
E
Scanziani
Annunciata
A
Vecchi
Emilio
E
Hirsch
Alberto
A
Mantovani
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D004751:Enteritis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000172:deficiency* / Q000235:genetics; D051193:Toll-Like Receptors
D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; C484529:SIGIRR protein, mouse