IL-2/IL-7-inducible factors pioneer the path to T cell differentiation in advance of lineage-defining factors.
EMBO J
; 39(22): e105220, 2020 11 16.
Article
em En
| MEDLINE
| ID: mdl-32930455
ABSTRACT
When dormant naïve T cells first become activated by antigen-presenting cells, they express the autocrine growth factor IL-2 which transforms them into rapidly dividing effector T cells. During this process, hundreds of genes undergo epigenetic reprogramming for efficient activation, and also for potential reactivation after they return to quiescence as memory T cells. However, the relative contributions of IL-2 and T cell receptor signaling to this process are unknown. Here, we show that IL-2 signaling is required to maintain open chromatin at hundreds of gene regulatory elements, many of which control subsequent stimulus-dependent alternative pathways of T cell differentiation. We demonstrate that IL-2 activates binding of AP-1 and STAT5 at sites that can subsequently bind lineage-determining transcription factors, depending upon what other external factors exist in the local T cell environment. Once established, priming can also be maintained by the stroma-derived homeostatic cytokine IL-7, and priming diminishes if Il7r is subsequently deleted in vivo. Hence, IL-2 is not just a growth factor; it lays the foundation for T cell differentiation and immunological memory.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator VII
/
Diferenciação Celular
/
Interleucina-7
/
Interleucina-2
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido