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.
Garlanda
Cecilia
C
Department of Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milan, Italy.
Riva
Federica
F
Polentarutti
Nadia
N
Buracchi
Chiara
C
Sironi
Marina
M
De Bortoli
Maida
M
Muzio
Marta
M
Bergottini
Raffaella
R
Scanziani
Eugenio
E
Vecchi
Annunciata
A
Hirsch
Emilio
E
Mantovani
Alberto
A
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