MicroRNAs of the miR-17â¼92 family are critical regulators of T(FH) differentiation.
Nat Immunol
; 14(8): 849-57, 2013 Aug.
Article
em 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
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Linfócitos B
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Diferenciação Celular
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Linfócitos T Auxiliares-Indutores
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Fosfoproteínas Fosfatases
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Centro Germinativo
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MicroRNAs
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos