Interleukin 23 Production by Intestinal CD103+CD11b+ Dendritic Cells in Response to Bacterial Flagellin Enhances Mucosal Innate Immune Defense.
Kinnebrew, Melissa A. 1; Buffie, Charlie G. 1; Diehl, Gretchen E. 2; Zenewicz, Lauren A. 3; Leiner, Ingrid 1; Hohl, Tobias M. 4; Flavell, Richard A. 3,5; Littman, Dan R. 2,5; Pamer, Eric G. 1,*
[Article]
Immunity.
36(2):276-287, February 2012.
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SUMMARY: Microbial penetration of the intestinal epithelial barrier triggers inflammatory responses that include induction of the bactericidal C-type lectin RegIII[gamma]. Systemic administration of flagellin, a bacterial protein that stimulates Toll-like receptor 5 (TLR5), induces epithelial expression of RegIII[gamma] and protects mice from intestinal colonization with antibiotic-resistant bacteria. Flagellin-induced RegIII[gamma] expression is IL-22 dependent, but how TLR signaling leads to IL-22 expression is incompletely defined. By 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 after bacterial flagellin administration and drove IL-22-dependent RegIII[gamma] production. Maximal expression of IL-23 subunits IL-23p19 and IL-12p40 occurred within 60 min of exposure to flagellin. IL-23 subsequently induced a burst of IL-22 followed by sustained RegIII[gamma] 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.
(C) 2012Elsevier, Inc.