The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells. (original) (raw)
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Immunity | 2012
Mice lacking the transcription factor T-bet in the innate immune system develop microbiota-dependent colitis. Here, we show that interleukin-17A (IL-17A)-producing IL-7Rα(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice. TNF-α produced by CD103(-)CD11b(+) dendritic cells synergized with IL-23 to drive IL-17A production by ILCs, demonstrating a previously unrecognized layer of cellular crosstalk between dendritic cells and ILCs. We have identified Helicobacter typhlonius as a key disease trigger driving excess TNF-α production and promoting colitis in TRUC mice. Crucially, T-bet also suppressed the expression of IL-7R, a key molecule involved in controlling intestinal ILC homeostasis. The importance of IL-7R signaling in TRUC disease was highlighted by the dramatic reduction in intestinal ILCs and attenuated colitis following IL-7R blockade. Taken together, these data demonstrate the mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota.
Pubmed ID: 23063332 RIS Download
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Associated grants
- Agency: Wellcome Trust, United Kingdom
Id: WT088747MA - Agency: Department of Health, United Kingdom
Id: DRF-2009-02-22 - Agency: Medical Research Council, United Kingdom
Id: G0600081 - Agency: Medical Research Council, United Kingdom
Id: G0802068 - Agency: Wellcome Trust, United Kingdom
Id: WT076964 - Agency: Medical Research Council, United Kingdom
Id: MR/J011118/1 - Agency: Medical Research Council, United Kingdom
Id: MR/J006742/1 - Agency: Medical Research Council, United Kingdom
Id: MR/K002996/1
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