TCF-1 limits the formation of Tc17 cells via repression of the MAF-ROR{gamma}t axis

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)-–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 RORt, 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 RORt. 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.

Source: The Journal of Experimental Medicine - June 30, 2019 Category: Internal Medicine Authors: 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., Godf Tags: Hematopoiesis Articles Source Type: research