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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Available from: Tobias M Hohl, Sep 30, 2015
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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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    • "Finally, increased penetration of commensal flora into the tumor as a result of diminished intestinal integrity in a mouse model of colorectal tumorigenesis has also been shown to sustain tumor growth through the activation of TLRs (Grivennikov et al., 2012). In particular, bacterial components such as flagellin bind to TLR5 and promote the release of the proinflammatory cytokine IL-23 (Kinnebrew et al., 2012), which is highly expressed in both mouse and human intestinal tumors (Grivennikov et al., 2012). When IL-23 is constitutively released at a high level, it promotes a state of chronic inflammation, which can abet the growth of the tumors (Grivennikov et al., 2012; Figure 3). "
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