TCF-1 limits the formation of Tc17 cells via repression of the MAF-RORgammat axis
- Mielke, LA; Liao, Y; Clemens, EB; Firth, MA; Duckworth, B; Huang, Q; Almeida, FF; Chopin, M; Koay, HF; Bell, CA; Hediyeh-Zadeh, S; Park, SL; Raghu, D; Choi, J; Putoczki, TL; Hodgkin, PD; Franks, AE; Mackay, LK; Godfrey, DI; Davis, MJ; Xue, HH; Bryant, VL; Kedzierska, K; Shi, W; Belz, GT;
- Journal Title
- Journal of Experimental Medicine
- Publication Type
- Journal Article in press
- 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)-gamma-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 RORgammat, 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 RORgammat 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.
- Rockefeller University Press
- WEHI Research Division(s)
- Bioinformatics; Immunology; Personalised Oncology
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-06-14 09:37:01Last Modified: 2019-06-14 11:24:13