Interleukin 23 Production by Intestinal CD103 +CD11b + Dendritic Cells in Response to Bacterial Flagellin Enhances Mucosal Innate Immune Defense

Infectious Diseases Service, Department of Medicine, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Immunity (Impact Factor: 21.56). 02/2012; 36(2):276-87. DOI: 10.1016/j.immuni.2011.12.011
Source: PubMed


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. 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 RegIIIγ 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 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.

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    • "Crosstalk between these macrophages and ILC3 instructed CD103 + DCs to produce RA, which in turn contributed to intestinal homeostasis (Mortha et al., 2014). Another study demonstrated that CD103 + DCs are a cellular source of IL-23, which have been demonstrated to interact and activate ILCs in a transient manner (Kinnebrew et al., 2012). Our data suggest that RA is an important regulator of ILC1 to ILC3 conversion. "
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    Immunity 07/2015; 43(1). DOI:10.1016/j.immuni.2015.06.019 · 21.56 Impact Factor
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    • "For example, murine lung CD11b + cDC2 are the primary drivers of Th2 responses following exposure to house dust mite allergens [82] [95], and of Th17 immunity , through release of IL-23, both in the steady state and during Aspergillus fumigatus infection [40]. A subset of mouse CD11b + cDC2 also expresses CD103; these cells, which are unique to the intestine, produce the Th17-inducing cytokines IL-6 and IL-23 in steady state or following Citrobacter rodentium infection or following immunization with a TLR5 ligand [40] [42] [96], and also migrate to LNs where they induce Th1/17 (IL-17 "
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    Cellular Immunology 09/2014; 291(1-2). DOI:10.1016/j.cellimm.2014.08.006 · 1.92 Impact Factor
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    • "Loss of these cells, however, does not alter intestinal T cell homeostasis or lead to spontaneous inflammation (Edelson et al., 2010). CD103 + CD11b + DCs, in contrast, require Notch2 signaling, produce IL-23 in response to flagellin-induced TLR5 activation, resulting in IL-22 production by ILC3, and have additionally been proposed to support Th17 polarization (Lewis et al., 2011; Kinnebrew et al., 2012). These cells can produce retinoic acid, which promotes the expression of the gut-homing receptor CCR9 and synergizes with TGF to induce regulatory T cells (Sun et al., 2007). "
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