Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells.
Proc Natl Acad Sci U S A
; 114(48): 12797-12802, 2017 11 28.
Article
em En
| MEDLINE
| ID: mdl-29133396
ABSTRACT
Follicular helper T cells (TFHs) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of TFH cells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFH program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFH cells and defined a TFH-specific miRNA signature. We report that hsa-miR-31-5p (miR-31) is down-regulated in TFH; we showed that BCL6 suppresses miR-31 expression by binding to its promoter; and we demonstrated that miR-31 inhibits the expression of molecules that control T-helper function, such as CD40L and SAP. These findings identify a BCL6-initiated inhibitory circuit that stabilizes the follicular helper T cell program at least in part through the control of miRNA transcription. Although BCL6 controls TFH activity in human and mouse, the role of miR-31 is restricted to human TFH cell differentiation, reflecting a species specificity of the miR-31 action. Our findings highlight miR-31 as a possible target to modulate human T cell dependent antibody responses in the settings of infection, vaccination, or immune dysregulation.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Linfócitos T Auxiliares-Indutores
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Ligante de CD40
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MicroRNAs
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Proteínas Proto-Oncogênicas c-bcl-6
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Proteína Associada à Molécula de Sinalização da Ativação Linfocitária
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Itália