TCF-1 limits the formation of Tc17 cells via repression of the MAF-RORγt axis.
J Exp Med
; 216(7): 1682-1699, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-31142588
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD8-Positivos
/
Interleucina-17
/
Proteínas Proto-Oncogênicas c-maf
/
Fator 1-alfa Nuclear de Hepatócito
/
Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Austrália