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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)12797-12802
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number48
DOIs
Publication statusPublished - Nov 28 2017

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Keywords

  • BCL6
  • Human CD4 T
  • MicroRNA
  • RNA-seq
  • Transcriptional regulation

ASJC Scopus subject areas

  • General

Cite this

Ripamonti, A., Provasi, E., Lorenzo, M., De Simone, M., Ranzani, V., Vangelisti, S., Curti, S., Bonnal, R. J. P., Pignataro, L., Torretta, S., Geginat, J., Rossetti, G., Pagani, M., & Abrignani, S. (2017). Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells. Proceedings of the National Academy of Sciences of the United States of America, 114(48), 12797-12802. https://doi.org/10.1073/pnas.1705364114