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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.
AuthorsNamiko Hoshi, Dominik Schenten, Simone A Nish, Zenta Walther, Nicola Gagliani, Richard A Flavell, Boris Reizis, Zeli Shen, James G Fox, Akiko Iwasaki, Ruslan Medzhitov
JournalNature communications (Nat Commun) Vol. 3 Pg. 1120 ( 2012) ISSN: 2041-1723 [Electronic] England
PMID23047678 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-1beta
  • Interleukin-23
  • Interleukin-6
  • Myeloid Differentiation Factor 88
  • Interleukin-10
Topics
  • Animals
  • Colitis (genetics, metabolism, pathology)
  • Colon (metabolism, pathology)
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Interleukin-10 (deficiency, genetics, metabolism)
  • Interleukin-1beta (metabolism)
  • Interleukin-23 (metabolism)
  • Interleukin-6 (metabolism)
  • Mice
  • Myeloid Differentiation Factor 88 (genetics, metabolism)
  • Phagocytes (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction (genetics, physiology)

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