MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/89148 https://orcid.org/0000-0001-9307-6116 |
| _version_ | 1811083532966035456 |
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| author | Hoshi, Namiko Schenten, Dominik Nish, Simone A. Walther, Zenta Gagliani, Nicola Flavell, Richard A. Reizis, Boris Shen, Zeli Fox, James G. Iwasaki, Akiko Medzhitov, Ruslan |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Hoshi, Namiko Schenten, Dominik Nish, Simone A. Walther, Zenta Gagliani, Nicola Flavell, Richard A. Reizis, Boris Shen, Zeli Fox, James G. Iwasaki, Akiko Medzhitov, Ruslan |
| author_sort | Hoshi, Namiko |
| collection | MIT |
| description | 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[superscript −/−] 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. |
| first_indexed | 2024-09-23T12:34:34Z |
| format | Article |
| id | mit-1721.1/89148 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:34:34Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/891482022-09-28T08:43:17Z MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice Hoshi, Namiko Schenten, Dominik Nish, Simone A. Walther, Zenta Gagliani, Nicola Flavell, Richard A. Reizis, Boris Shen, Zeli Fox, James G. Iwasaki, Akiko Medzhitov, Ruslan Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Shen, Zeli Fox, James G. 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[superscript −/−] 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. Howard Hughes Medical Institute National Institutes of Health (U.S.) (NIH grant DK071754) National Institutes of Health (U.S.) (NIH grant AI046688) National Institutes of Health (U.S.) (NIH grant AI055502) National Institutes of Health (U.S.) (NIH grant RO1OD011141) National Institutes of Health (U.S.) (Training grant) National Cancer Institute (U.S.) (Irvington Fellowship) 2014-09-03T14:37:29Z 2014-09-03T14:37:29Z 2012-10 2012-04 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/89148 Hoshi, Namiko, Dominik Schenten, Simone A. Nish, Zenta Walther, Nicola Gagliani, Richard A. Flavell, Boris Reizis, et al. “MyD88 Signalling in Colonic Mononuclear Phagocytes Drives Colitis in IL-10-Deficient Mice.” Nature Communications 3 (October 9, 2012): 1120. https://orcid.org/0000-0001-9307-6116 en_US http://dx.doi.org/10.1038/ncomms2113 Nature Communications Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Hoshi, Namiko Schenten, Dominik Nish, Simone A. Walther, Zenta Gagliani, Nicola Flavell, Richard A. Reizis, Boris Shen, Zeli Fox, James G. Iwasaki, Akiko Medzhitov, Ruslan MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice |
| title | MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice |
| title_full | MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice |
| title_fullStr | MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice |
| title_full_unstemmed | MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice |
| title_short | MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice |
| title_sort | myd88 signalling in colonic mononuclear phagocytes drives colitis in il 10 deficient mice |
| url | http://hdl.handle.net/1721.1/89148 https://orcid.org/0000-0001-9307-6116 |
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