The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema

Nat Immunol. 2015 Nov;16(11):1185-94. doi: 10.1038/ni.3292. Epub 2015 Oct 5.


Smoking-related emphysema is a chronic inflammatory disease driven by the T(H)17 subset of helper T cells through molecular mechanisms that remain obscure. Here we explored the role of the microRNA miR-22 in emphysema. We found that miR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism that involved the transcription factor NF-κB. Mice deficient in miR-22, but not wild-type mice, showed attenuated T(H)17 responses and failed to develop emphysema after exposure to smoke or nCB. We further found that miR-22 controlled the activation of APCs and T(H)17 responses through the activation of AP-1 transcription factor complexes and the histone deacetylase HDAC4. Thus, miR-22 is a critical regulator of both emphysema and T(H)17 responses.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Emphysema / etiology*
  • Emphysema / immunology
  • Emphysema / metabolism
  • Histone Deacetylases / metabolism
  • Humans
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism
  • Repressor Proteins / antagonists & inhibitors*
  • Smoking / adverse effects
  • Soot / toxicity
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Transcription Factor AP-1 / metabolism


  • MIRN22 microRNA, human
  • MicroRNAs
  • Mirn22 microRNA, mouse
  • NF-kappa B
  • Repressor Proteins
  • Soot
  • Transcription Factor AP-1
  • HDAC4 protein, human
  • Hdac5 protein, mouse
  • Histone Deacetylases

Associated data

  • GEO/GSE72734