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PMID: 23047678 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature communications ·Vol. 3 ·2012-00-00 ·Pages 1120

Hoshi N, Schenten D, Nish SA, Walther Z, Gagliani N, Flavell RA, Reizis B, Shen Z, Fox JG, Iwasaki A, Medzhitov R

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.

MeSH Terms
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
Chemicals
Interleukin-1beta Interleukin-23 Interleukin-6 Myeloid Differentiation Factor 88 Interleukin-10
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Hoshi Namiko
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Schenten Dominik
Nish Simone A
Walther Zenta
Gagliani Nicola
Flavell Richard A
Reizis Boris
Shen Zeli
Fox James G
Iwasaki Akiko
Medzhitov Ruslan
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms2113
Published
2012-00-00
Pages
1120
Language
English
Region
England
NLM ID
101528555
PMCID
PMC3521499
Subset
IM
Grants
NIH HHS · R01 OD011141 · United States
NIAID NIH HHS · AI055502 · United States
NIAID NIH HHS · R01 AI055502 · United States
Howard Hughes Medical Institute · United States
NIDDK NIH HHS · DK071754 · United States
NIAID NIH HHS · R37 AI046688 · United States
NIDDK NIH HHS · R01 DK071754 · United States
NIAID NIH HHS · R01 AI046688 · United States
NIH HHS · R01OD011141 · United States
NIAID NIH HHS · AI046688 · United States
NIEHS NIH HHS · P30 ES002109 · United States
External Links
PubMed source DOI: 10.1038/ncomms2113 PMC Full Text View journal details
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