MicroRNAs of the miR-17â¼92 family are critical regulators of T(FH) differentiation.
Nat Immunol
; 14(8): 849-57, 2013 Aug.
Article
en En
| MEDLINE
| ID: mdl-23812097
ABSTRACT
Follicular helper T cells (T(FH) cells) provide critical help to B cells during humoral immune responses. Here we report that mice with T cell-specific deletion of the miR-17â¼92 family of microRNAs (miRNAs) had substantially compromised T(FH) differentiation, germinal-center formation and antibody responses and failed to control chronic viral infection. Conversely, mice with T cell-specific expression of a transgene encoding miR-17â¼92 spontaneously accumulated T(FH) cells and developed a fatal immunopathology. Mechanistically, the miR-17â¼92 family controlled the migration of CD4(+) T cells into B cell follicles by regulating signaling intensity from the inducible costimulator ICOS and kinase PI(3)K by suppressing expression of the phosphatase PHLPP2. Our findings demonstrate an essential role for the miR-17â¼92 family in T(FH) differentiation and establish PHLPP2 as an important mediator of their function in this process.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Linfocitos B
/
Diferenciación Celular
/
Linfocitos T Colaboradores-Inductores
/
Fosfoproteínas Fosfatasas
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Centro Germinal
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MicroARNs
Límite:
Animals
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos