MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice

Namiko Hoshi, Dominik Schenten, Simone A. Nish, Zenta Walther, Nicola Gagliani, Richard A. Flavell, Boris Reizis, Zeli Shen, James G. Fox, Akiko Iwasaki, Ruslan Medzhitov

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


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.

Original languageEnglish (US)
Article number1120
JournalNature communications
StatePublished - 2012

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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