The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression

Nat Immunol. 2013 Aug;14(8):840-8. doi: 10.1038/ni.2642. Epub 2013 Jun 30.


Follicular helper T cells (TFH cells) are the prototypic helper T cell subset specialized to enable B cells to form germinal centers (GCs) and produce high-affinity antibodies. We found that expression of microRNAs (miRNAs) by T cells was essential for TFH cell differentiation. More specifically, we show that after immunization of mice with protein, the miRNA cluster miR-17∼92 was critical for robust differentiation and function of TFH cells in a cell-intrinsic manner that occurred regardless of changes in proliferation. In a viral infection model, miR-17∼92 restrained the expression of genes 'inappropriate' to the TFH cell subset, including the direct miR-17∼92 target Rora. Removal of one Rora allele partially 'rescued' the inappropriate gene signature in miR-17∼92-deficient TFH cells. Our results identify the miR-17∼92 cluster as a critical regulator of T cell-dependent antibody responses, TFH cell differentiation and the fidelity of the TFH cell gene-expression program.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • Arenaviridae Infections / immunology
  • Arenaviridae Infections / virology
  • Cell Differentiation / immunology*
  • Flow Cytometry
  • Gene Expression Regulation / immunology*
  • Immunohistochemistry
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / immunology*
  • Statistics, Nonparametric
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • MIRN17-92 microRNA, mouse
  • MicroRNAs
  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • Rora protein, mouse

Associated data

  • GEO/GSE42760