期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 216, 期 7, 页码 1682-1699出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20181778
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资金
- National Health and Medical Research Council (NHMRC) of Australia [1047903, 1049307, 1071916, 1127198]
- Priority-driven Collaborative Cancer Research Scheme
- Cancer Australia
- Cure Cancer Australia Foundation [1123388, 1050241]
- Rebecca L. Cooper Foundation Medical Research Foundation from the NHMRC [APP1135898, APP1160333, APP1106004, APP1117766, APP1102792]
- Victorian Cancer Agency
- Cancer Council Victoria Postdoctoral Fellowship
- Walter and Eliza Hall Innovation Centenary Fellowships - Commonwealth SerumLaboratories (CSL) Limited
- Dyson Bequest
- Walter and Eliza Hall Innovation grant
- Research Focus Area for Securing Food, Water and the Environment at La Trobe University
- National Health and Medical Research Council of Australia [1127198] Funding Source: NHMRC
Interleukin (IL)-17-producing CD8(+) T (Tc17) cells have emerged as key players in host-microbiota interactions, infection, and cancer. The factors that drive their development, in contrast to interferon (IFN)-gamma-producing effector CD8(+) T cells, are not clear. Here we demonstrate that the transcription factor TCF-1 (Tcf7) regulates CD8(+) T cell fate decisions in double-positive (DP) thymocytes through the sequential suppression of MAF and ROR gamma t, in parallel with TCF-1-driven modulation of chromatin state. Ablation of TCF-1 resulted in enhanced Tc17 cell development and exposed a gene set signature to drive tissue repair and lipid metabolism, which was distinct from other CD8(+) T cell subsets. IL-17-producing CD8(+) T cells isolated from healthy humans were also distinct from CD8(+)IL-17(-) T cells and enriched in pathways driven by MAF and ROR gamma t. Overall, our study reveals how TCF-1 exerts central control of T cell differentiation in the thymus by normally repressing Tc17 differentiation and promoting an effector fate outcome.
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