Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/134873
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Type: | Journal article |
Title: | TCF-1 limits the formation of Tc17 cells via repression of the MAF–RORγt axis |
Author: | Mielke, L.A. Liao, Y. Clemens, E.B. Firth, M.A. Duckworth, B. Huang, Q. Almeida, F.F. Chopin, M. Koay, H.F. Bell, C.A. Hediyeh-Zadeh, S. Park, S.L. Raghu, D. Choi, J. Putoczki, T.L. Hodgkin, P.D. Franks, A.E. Mackay, L.K. Godfrey, D.I. Davis, M.J. et al. |
Citation: | Journal of Experimental Medicine, 2019; 216(7):1682-1699 |
Publisher: | Rockefeller University Press |
Issue Date: | 2019 |
ISSN: | 0022-1007 1540-9538 |
Statement of Responsibility: | Lisa A. Mielke ... Melissa J. Davis ... et. al |
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. |
Keywords: | Hematopoiesis |
Rights: | © 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/). |
DOI: | 10.1084/jem.20181778 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1106004 http://purl.org/au-research/grants/nhmrc/1117766 http://purl.org/au-research/grants/nhmrc/1047903 http://purl.org/au-research/grants/nhmrc/1049307 http://purl.org/au-research/grants/nhmrc/1160333 http://purl.org/au-research/grants/nhmrc/1071916 http://purl.org/au-research/grants/nhmrc/1127198 http://purl.org/au-research/grants/nhmrc/1102792 http://purl.org/au-research/grants/nhmrc/1135898 |
Published version: | http://dx.doi.org/10.1084/jem.20181778 |
Appears in Collections: | Medicine publications |
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hdl_134873.pdf | Published version | 3.73 MB | Adobe PDF | View/Open |
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