| First Author | Powell N | Year | 2012 |
| Journal | Immunity | Volume | 37 |
| Issue | 4 | Pages | 674-84 |
| PubMed ID | 23063332 | Mgi Jnum | J:188554 |
| Mgi Id | MGI:5441105 | Doi | 10.1016/j.immuni.2012.09.008 |
| Citation | Powell N, et al. (2012) The Transcription Factor T-bet Regulates Intestinal Inflammation Mediated by Interleukin-7 Receptor(+) Innate Lymphoid Cells. Immunity 37(4):674-84 |
| abstractText | 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-7Ralpha(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice. TNF-alpha 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-alpha 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. |
