期刊
IMMUNITY
卷 49, 期 6, 页码 1077-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2018.10.014
关键词
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类别
资金
- Crohn's and Colitis Foundation Senior Research Award
- NIH [1R03DK111852, 1R01 DK114252]
- USPHS [DK056328]
- NIH Medical Scientist Training Program [T32GM07739]
- F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute
- NIH K08 Career Development Award [DK099381, DK093578]
- [NIHR01AI125264]
Inflammatory bowel disease (IBD) results from a dys-regulated interaction between the microbiota and a genetically susceptible host. Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A is not known. Here, we found that adherent IBD-associated microbiota induced TL1A release from CX3CR1(+) mononuclear phagocytes (MNPs). Using cell-specific genetic deletion models, we identified an essential role for CX3CR1(+)MNP-derived TL1A in driving group 3 innate lymphoid cell (ILC3) production of interleukin-22 and mucosal healing during acute colitis. In contrast to this protective role in acute colitis, TL1A-dependent expression of co-stimulatory molecule OX40L in MHCII+ ILC3s during colitis led to co-stimulation of antigen-specific T cells that was required for chronic T cell colitis. These results identify a role for ILC3s in activating intestinal T cells and reveal a central role for TL1A in promoting ILC3 barrier immunity during colitis.
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