Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells
Articolo
Data di Pubblicazione:
2017
Citazione:
Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells / A. Ripamonti, E. Provasi, M. Lorenzo, M. De Simone, V. Ranzani, S. Vangelisti, S. Curti, R.J.P. Bonnal, L. Pignataro, S. Torretta, J. Geginat, G. Rossetti, M. Pagani, S. Abrignani. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 114:48(2017 Nov 28), pp. 12797-12802. [10.1073/pnas.1705364114]
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 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
BCL6; Human CD4+TFH; MicroRNA; RNA-seq; Transcriptional regulation; Multidisciplinary
Elenco autori:
A. Ripamonti, E. Provasi, M. Lorenzo, M. De Simone, V. Ranzani, S. Vangelisti, S. Curti, R.J.P. Bonnal, L. Pignataro, S. Torretta, J. Geginat, G. Rossetti, M. Pagani, S. Abrignani, M. Pagani
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