TCF-1 limits the formation of Tc17 cells via repression of the MAF-RORγt axis Academic Article uri icon

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.

authors

  • Mielke, Lisa A
  • Liao, Yang
  • Clemens, Ella Bridie
  • Firth, Matthew A
  • Duckworth, Brigette
  • Huang, Qiutong
  • Almeida, Francisca F
  • Chopin, Michael
  • Koay, Hui-Fern
  • Bell, Carolyn A
  • Hediyeh-Zadeh, Soroor
  • Park, Simone L
  • Raghu, Dinesh
  • Choi, Jarny
  • Putoczki, Tracy L
  • Hodgkin, Philip D
  • Franks, Ashley E
  • Mackay, Laura K
  • Godfrey, Dale
  • Davis, Melissa J
  • Xue, Hai-Hui
  • Bryant, Vanessa L
  • Kedzierska, Katherine
  • Shi, Wei
  • Belz, Gabrielle T

publication date

  • 2019