Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells.

Follicular helper T cells (Ts) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of T cells are controlled by the master gene , but it is largely unclear how this transcription repressor specifies the T program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in T cells and defined a T-specific miRNA signature. We report that hsa-miR-31-5p (miR-31) is down-regulated in T; 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 T activity in human and mouse, the role of miR-31 is restricted to human T 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.