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Intestinal CD103+ CD11b+ lamina propria dendritic cells instruct intestinal epithelial cells to express antimicrobial proteins in response to Toll-like receptor 5 activation

Microbial penetration of the intestinal epithelial barrier triggers inflammatory responses that include induction of the bactericidal C-type lectin RegIIIγ. Systemic administration of flagellin, a bacterial protein that stimulates Toll-like receptor 5 (TLR5), induces epithelial expression of RegIIIγ...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2012-02, Vol.36 (2), p.276-287
Main Authors: Kinnebrew, Melissa A., Buffie, Charlie G., Diehl, Gretchen E., Zenewicz, Lauren A., Leiner, Ingrid, Hohl, Tobias M., Flavell, Richard A., Littman, Dan R., Pamer, Eric G.
Format: Article
Language:English
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Summary:Microbial penetration of the intestinal epithelial barrier triggers inflammatory responses that include induction of the bactericidal C-type lectin RegIIIγ. Systemic administration of flagellin, a bacterial protein that stimulates Toll-like receptor 5 (TLR5), induces epithelial expression of RegIIIγ and protects mice from intestinal colonization with antibiotic-resistant bacteria. Flagellin-induced RegIIIγ expression is IL-22-dependent, but how TLR signaling leads to IL-22 expression is incompletely defined. Using conditional depletion of lamina propria dendritic cell (LPDC) subsets, we demonstrated that CD103 + CD11b + LPDCs, but not monocyte-derived CD103 − CD11b + LPDCs, expressed high amounts of IL-23 following bacterial flagellin administration and drove IL-22-dependent RegIIIγ production. Maximal expression of IL-23 subunits IL-23p19 and IL-12p40 occurred within 60 minutes of exposure to flagellin. IL-23 subsequently induced a burst of IL-22 followed by sustained RegIIIγ expression. Thus, CD103 + CD11b + LPDCs, in addition to promoting long-term tolerance to ingested antigens, also rapidly produce IL-23 in response to detection of flagellin in the lamina propria.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2011.12.011