MicroRNAs of the miR-17∼92 family are critical regulators of T(FH) differentiation

Nat Immunol. 2013 Aug;14(8):849-57. doi: 10.1038/ni.2648. Epub 2013 Jun 30.


Follicular helper T cells (T(FH) cells) provide critical help to B cells during humoral immune responses. Here we report that mice with T cell-specific deletion of the miR-17∼92 family of microRNAs (miRNAs) had substantially compromised T(FH) differentiation, germinal-center formation and antibody responses and failed to control chronic viral infection. Conversely, mice with T cell-specific expression of a transgene encoding miR-17∼92 spontaneously accumulated T(FH) cells and developed a fatal immunopathology. Mechanistically, the miR-17∼92 family controlled the migration of CD4(+) T cells into B cell follicles by regulating signaling intensity from the inducible costimulator ICOS and kinase PI(3)K by suppressing expression of the phosphatase PHLPP2. Our findings demonstrate an essential role for the miR-17∼92 family in T(FH) differentiation and establish PHLPP2 as an important mediator of their function in this process.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Flow Cytometry
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Immunity, Humoral / immunology
  • Immunohistochemistry
  • Inducible T-Cell Co-Stimulator Protein / immunology
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs / immunology*
  • Nuclear Proteins / immunology*
  • Phosphatidylinositol 3-Kinases / immunology
  • Phosphoprotein Phosphatases / immunology*
  • Signal Transduction / immunology
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / enzymology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Icos protein, mouse
  • Inducible T-Cell Co-Stimulator Protein
  • MIRN17-92 microRNA, mouse
  • MicroRNAs
  • Nuclear Proteins
  • PHLPP1 protein, mouse
  • Phosphoprotein Phosphatases