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 TFHcells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFHprogram. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFHcells and defined a TFH-specific miRNA signature. We report that hsaâmiR-31â5p (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 TFHactivity in human and mouse, the role of miR-31 is restricted to human TFHcell 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.
|Titolo:||Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells|
|Parole Chiave:||BCL6; Human CD4+TFH; MicroRNA; RNA-seq; Transcriptional regulation; Multidisciplinary|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||28-nov-2017|
|Digital Object Identifier (DOI):||10.1073/pnas.1705364114|
|Appare nelle tipologie:||01 - Articolo su periodico|