Abstract
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.
Original language | English |
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Pages (from-to) | 674-684 |
Number of pages | 11 |
Journal | Immunity |
Volume | 37 |
Issue number | 4 |
DOIs | |
Publication status | Published - 19 Oct 2012 |
Bibliographical note
Copyright © 2012 Elsevier Inc. All rights reserved.Keywords
- animals
- cells, cultured
- chronic disease
- colitis, ulcerative
- DNA-binding proteins
- helicobacter
- immunity, innate
- lymphocytes
- mice
- mice, inbred BALB C
- mice, knockout
- receptors, interleukin-7
- signal transduction
- t-box domain proteins