TCF-1 limits the formation of Tc17 cells via repression of the MAF–RORγt axis

LA Mielke; Y Liao; EB Clemens; MA Firth; B Duckworth; Q Huang; FF Almeida; M Chopin; HF Koay; CA Bell; S Hediyeh-Zadeh; SL Park; D Raghu; J Choi; TL Putoczki; PD Hodgkin; AE Franks; LK Mackay; DI Godfrey; MJ Davis; HH Xue; VL Bryant; K Kedzierska; W Shi; GT Belz

Journal article

TCF-1 limits the formation of Tc17 cells via repression of the MAF–RORγt axis

LA Mielke, Y Liao, EB Clemens, MA Firth, B Duckworth, Q Huang, FF Almeida, M Chopin, HF Koay, CA Bell, S Hediyeh-Zadeh, SL Park, D Raghu, J Choi, TL Putoczki, PD Hodgkin, AE Franks, LK Mackay, DI Godfrey, MJ Davis Show all

Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2019

DOI: 10.1084/jem.20181778

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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-..

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University of Melbourne Researchers

Bridie Clemens Author

Fern Koay Author

Simone Park Author

Jarny Choi Author

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Awarded by Cancer Council Victoria

Funding Acknowledgements

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 SerumLaboratories (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.