MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production

Immunity. 2016 Apr 19;44(4):821-32. doi: 10.1016/j.immuni.2016.01.003. Epub 2016 Feb 2.

Abstract

MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary T cells uncovered multiple miRNAs that inhibited Th2 cell differentiation. Among these were miR-24 and miR-27, miRNAs coexpressed from two genomic clusters, which each functioned independently to limit interleukin-4 (IL-4) production. Mice lacking both clusters in T cells displayed increased Th2 cell responses and tissue pathology in a mouse model of asthma. Gene expression and pathway analyses placed miR-27 upstream of genes known to regulate Th2 cells. They also identified targets not previously associated with Th2 cell biology which regulated IL-4 production in unbiased functional testing. Thus, elucidating the biological function and target repertoire of miR-24 and miR-27 reveals regulators of Th2 cell biology.

Publication types

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

MeSH terms

  • Animals
  • Asthma / immunology*
  • Base Sequence
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Inflammation / immunology
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics*
  • Multigene Family / genetics
  • Sequence Analysis, RNA
  • Th2 Cells / cytology
  • Th2 Cells / immunology*

Substances

  • MicroRNAs
  • Mirn24 microRNA, mouse
  • Mirn27 microRNA, mouse
  • Interleukin-4