TCF-1 limits the formation of Tc17 cells via repression of the MAF–RORγt axis
| العنوان: | TCF-1 limits the formation of Tc17 cells via repression of the MAF–RORγt axis |
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| المؤلفون: | Matthew A. Firth, Hai-Hui Xue, Laura K. Mackay, Tracy L Putoczki, Dinesh Raghu, Philip D. Hodgkin, Yang Liao, Qiutong Huang, Simone L Park, Brigette C. Duckworth, Ashley E. Franks, Dale I. Godfrey, Lisa A. Mielke, Melissa J. Davis, Michael Chopin, Soroor Hediyeh-Zadeh, Katherine Kedzierska, Vanessa L. Bryant, Gabrielle T. Belz, Wei Shi, Francisca F. Almeida, Jarny Choi, Ella Bridie Clemens, Carolyn A. Bell, Hui-Fern Koay |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, T cell, Immunology, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, T-Lymphocyte Subsets, Interferon, medicine, Animals, Humans, Immunology and Allergy, Hepatocyte Nuclear Factor 1-alpha, Transcription factor, Research Articles, Mice, Knockout, Cell growth, Chemistry, Interleukin-17, Nuclear Receptor Subfamily 1, Group F, Member 3, Flow Cytometry, Lipid Metabolism, Chromatin, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Proto-Oncogene Proteins c-maf, 030220 oncology & carcinogenesis, T cell differentiation, Chromatin Immunoprecipitation Sequencing, Interleukin 17, CD8, medicine.drug |
| الوصف: | Mielke et al. show that TCF-1 limits IL-17–producing CD8+ T (Tc17) cell development from double-positive thymocytes through the sequential suppression of MAF and RORγt, while cementing conventional CD8+ T cell fate. 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)-γ–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 RORγt, 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 RORγt. 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. |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b96e17fb85c4cee737314c511398a22bTest https://doi.org/10.1084/jem.20181778Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b96e17fb85c4cee737314c511398a22b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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