The E3 ubiquitin ligase Itch is required for the differentiation of follicular helper T cells.
Nat Immunol
; 15(7): 657-66, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24859451
ABSTRACT
Follicular helper T cells (T(FH) cells) are responsible for effective B cell-mediated immunity, and Bcl-6 is a central factor for the differentiation of T(FH) cells. However, the molecular mechanisms that regulate the induction of T(FH) cells remain unclear. Here we found that the E3 ubiquitin ligase Itch was essential for the differentiation of T(FH) cells, germinal center responses and immunoglobulin G (IgG) responses to acute viral infection. Itch acted intrinsically in CD4(+) T cells at early stages of T(FH) cell development. Itch seemed to act upstream of Bcl-6 expression, as Bcl-6 expression was substantially impaired in Itch(-/-) cells, and the differentiation of Itch(-/-) T cells into T(FH) cells was restored by enforced expression of Bcl-6. Itch associated with the transcription factor Foxo1 and promoted its ubiquitination and degradation. The defective T(FH) differentiation of Itch(-/-) T cells was rectified by deletion of Foxo1. Thus, our results indicate that Itch acts as an essential positive regulator in the differentiation of T(FH) cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Linfócitos T Auxiliares-Indutores
/
Ubiquitina-Proteína Ligases
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos