| First Author | Mielke LA | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 7 | Pages | 1682-1699 |
| PubMed ID | 31142588 | Mgi Jnum | J:280070 |
| Mgi Id | MGI:6364258 | Doi | 10.1084/jem.20181778 |
| Citation | Mielke LA, et al. (2019) TCF-1 limits the formation of Tc17 cells via repression of the MAF-RORgammat axis. J Exp Med 216(7):1682-1699 |
| abstractText | 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. |
