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Title: TCF-1 limits the formation of Tc17 cells via repression of the MAF-RORγt axis.
Austin Authors: Mielke, Lisa A;Liao, Yang;Clemens, Ella Bridie;Firth, Matthew A;Duckworth, Brigette;Huang, Qiutong;Almeida, Francisca F;Chopin, Michael;Koay, Hui-Fern;Bell, Carolyn A;Hediyeh-Zadeh, Soroor;Park, Simone L;Raghu, Dinesh;Choi, Jarny;Putoczki, Tracy L;Hodgkin, Philip D;Franks, Ashley E;Mackay, Laura K;Godfrey, Dale I;Davis, Melissa J;Xue, Hai-Hui;Bryant, Vanessa L;Kedzierska, Katherine;Shi, Wei;Belz, Gabrielle T
Affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Department of Medical Biology, University of Melbourne, Parkville, Australia
La Trobe University School of Cancer Medicine, Heidelberg, Australia
Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia
Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Australia
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia
Centre for Future Landscapes, La Trobe University, Bundoora, Australia
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
Department of Clinical Immunology & Allergy, The Royal Melbourne Hospital, Parkville, Australia
Department of Computing and Information Systems, University of Melbourne, Parkville, Australia
Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA
Issue Date: 1-Jul-2019
Date: 2019-05-29
Publication information: The Journal of experimental medicine 2019; 216(7): 1682-1699
Abstract: 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.
DOI: 10.1084/jem.20181778
ORCID: 0000-0002-9522-9320
Journal: The Journal of experimental medicine
PubMed URL: 31142588
Type: Journal Article
Appears in Collections:Journal articles

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