The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote TH17 cell-dependent emphysema

Wen Lu, Ran You, Xiaoyi Yuan, Tianshu Yang, Errol L G Samuel, Daniela C. Marcano, William K A Sikkema, James M. Tour, Antony Rodriguez, Farrah Kheradmand, David B. Corry

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1185-1194
Number of pages10
JournalNature immunology
Volume16
Issue number11
DOIs
StatePublished - Oct 20 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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