Anti-inflammatory Roles of Glucocorticoids Are Mediated by Foxp3+ Regulatory T Cells via a miR-342-Dependent Mechanism

Immunity. 2020 Sep 15;53(3):581-596.e5. doi: 10.1016/j.immuni.2020.07.002. Epub 2020 Jul 23.


Glucocorticoids (GC) are the mainstay treatment option for inflammatory conditions. Despite the broad usage of GC, the mechanisms by which GC exerts its effects remain elusive. Here, utilizing murine autoimmune and allergic inflammation models, we report that Foxp3+ regulatory T (Treg) cells are irreplaceable GC target cells in vivo. Dexamethasone (Dex) administered in the absence of Treg cells completely lost its ability to control inflammation, and the lack of glucocorticoid receptor in Treg cells alone resulted in the loss of therapeutic ability of Dex. Mechanistically, Dex induced miR-342-3p specifically in Treg cells and miR-342-3p directly targeted the mTORC2 component, Rictor. Altering miRNA-342-3p or Rictor expression in Treg cells dysregulated metabolic programming in Treg cells, controlling their regulatory functions in vivo. Our results uncover a previously unknown contribution of Treg cells during glucocorticoid-mediated treatment of inflammation and the underlying mechanisms operated via the Dex-miR-342-Rictor axis.

Keywords: Treg cells; allergic inflammation; autoimmune inflammation; glucocorticoids; metabolism; miRNA.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Dexamethasone / pharmacology*
  • Forkhead Transcription Factors / metabolism
  • Glucocorticoids / pharmacology*
  • Inflammation / drug therapy*
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Rapamycin-Insensitive Companion of mTOR Protein / metabolism*
  • Receptors, Glucocorticoid / genetics
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • Anti-Inflammatory Agents
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Glucocorticoids
  • MicroRNAs
  • Mirn342 microRNA, mouse
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Receptors, Glucocorticoid
  • rictor protein, mouse
  • Dexamethasone
  • Mechanistic Target of Rapamycin Complex 2