期刊
IMMUNITY
卷 41, 期 2, 页码 244-256出版社
CELL PRESS
DOI: 10.1016/j.immuni.2014.06.017
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资金
- Ellison Medical Foundation New Scholar Award in Aging
- Irma T. Hirschl Award
- Crohn's & Colitis Foundation of America Senior Research Award
- National Institutes of Health NIH [R01 DK093674-02]
- Leona M. and Harry B. Helmsley Charitable Trust
- Dutch Digestive Foundation
- NIH [R00DK088589]
- FCCC-Temple University Nodal grant
- Pew Scholar in Biomedical Sciences Program
The intestinal epithelium harbors large populations of activated and memory lymphocytes, yet these cells do not cause tissue damage in the steady state. We investigated how intestinal T cell effector differentiation is regulated upon migration to the intestinal epithelium. Using gene loss-and gain-of-function strategies, as well as reporter approaches, we showed that cooperation between the transcription factors T-bet and Runx3 resulted in suppression of conventional CD4(+) T helper functions and induction of an intraepithelial lymphocyte (IEL) program that included expression of IEL markers such as CD8 alpha alpha homodimers. Interferon-gamma sensing and T-bet expression by CD4(+) T cells were both required for this program, which was distinct from conventional T helper differentiation but shared by other IEL populations, including TCR alpha beta(+)CD8 alpha alpha(+) IELs. We conclude that the gut environment provides cues for IEL maturation through the interplay between T-bet and Runx3, allowing tissue-specific adaptation of mature T lymphocytes.
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