title: MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice.
abstract: Commensal bacterial sensing by Toll-like receptors is critical for maintaining intestinal homeostasis, but can lead to colitis in the absence of interleukin-10. Although Toll-like receptors are expressed in multiple cell types in the colon, the cell type(s) responsible for the development of colitis are currently unknown. Here we generated mice that are selectively deficient in MyD88 in various cellular compartments in an interleukin-10(-/-) setting. Although epithelial expression of MyD88 was dispensable, MyD88 expression in the mononuclear phagocyte compartment was required for colitis development. Specifically, phenotypically distinct populations of colonic mononuclear phagocytes expressed high levels of interleukin-1β, interleukin-23 and interleukin-6, and promoted T-helper 17 responses in the absence of interleukin-10. Thus, gut bacterial sensing through MyD88 in mononuclear phagocytes drives inflammatory bowel disease when unopposed by interleukin-10.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Namiko
authors.initials: N
authors.lastname: Hoshi
authors.forename: Dominik
authors.initials: D
authors.lastname: Schenten
authors.forename: Simone A
authors.initials: SA
authors.lastname: Nish
authors.forename: Zenta
authors.initials: Z
authors.lastname: Walther
authors.forename: Nicola
authors.initials: N
authors.lastname: Gagliani
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.forename: Zeli
authors.initials: Z
authors.lastname: Shen
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Ruslan
authors.initials: R
authors.lastname: Medzhitov
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D053594:Myeloid Differentiation Factor 88; D016753:Interleukin-10