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

Dongkyun Kim, Quang Tam Nguyen, Juyeun Lee, Sung Hwan Lee, Allison Janocha, Sohee Kim, Hongnga T. Le, Nina Dvorina, Kelly Weiss, Mark J. Cameron, Kewal Asosingh, Serpil C. Erzurum, William M. Baldwin, Ju Seog Lee, Booki Min*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)581-596.e5
JournalImmunity
Volume53
Issue number3
DOIs
StatePublished - Sep 15 2020
Externally publishedYes

Keywords

  • Treg cells
  • allergic inflammation
  • autoimmune inflammation
  • glucocorticoids
  • metabolism
  • miRNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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