@article{f0500cf0d19d41388dd73f1fce2db634,
title = "TCF-1 limits the formation of Tc17 cells via repression of the MAF–RORγt axis",
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.",
author = "Mielke, {Lisa A.} and Yang Liao and Clemens, {Ella Bridie} and Firth, {Matthew A.} and Brigette Duckworth and Qiutong Huang and Almeida, {Francisca F.} and Michael Chopin and Koay, {Hui Fern} and Bell, {Carolyn A.} and Soroor Hediyeh-Zadeh and Park, {Simone L.} and Dinesh Raghu and Jarny Choi and Putoczki, {Tracy L.} and Hodgkin, {Philip D.} and Franks, {Ashley E.} and Mackay, {Laura K.} and Godfrey, {Dale I.} and Davis, {Melissa J.} and Xue, {Hai Hui} and Bryant, {Vanessa L.} and Katherine Kedzierska and Wei Shi and Belz, {Gabrielle T.}",
note = "Funding Information: Financial support for this work was provided by National Health and Medical Research Council (NHMRC) of Australia grants (1047903 and 1049307 to L.A. Mielke and G.T. Belz, 1071916 to K. Kedzierska, and 1127198 to P.D. Hodgkin and V.L. Bryant), grants awarded through the Priority-driven Collaborative Cancer Research Scheme and co-funded by the Cancer Australia and Cure Cancer Australia Foundation (1123388 and 1050241), the Rebecca L. Cooper Foundation Medical Research Foundation (G.T. Belz), fellowships from the NHMRC (G.T. Belz, APP1135898; E.B. Clemens, Peter Doherty Fellow; H-F. Koay, APP1160333; L.K. Mackay, APP1106004; D.I. Godfrey, APP1117766; and K. Kedzierska, APP1102792), the Victorian Cancer Agency (T.L. Putoczki and L.A. Mielke), the Cancer Council Victoria Postdoctoral Fellowship (S.L. Park), Walter and Eliza Hall Innovation Centenary Fellowships sponsored by the Commonwealth Serum Laboratories (CSL) Limited (W. Shi) and the Dyson Bequest (T.L. Putoczki), and a Walter and Eliza Hall Innovation grant (W. Shi). A.E. Franks and C.A. Bell are supported by the Research Focus Area for Securing Food, Water and the Environment at La Trobe University. This study was made possible through Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institute Infrastructure Support scheme. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2019 Crown copyright. The government of Australia, Canada, or the UK ({"}the Crown{"}) owns the copyright interests of authors who are government employees. The Crown Copyright is not transferable. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).",
year = "2019",
month = jul,
doi = "10.1084/jem.20181778",
language = "English",
volume = "216",
pages = "1682--1699",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "The Rockefeller University Press",
number = "7",
}
