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

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

Author information

1
Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas, USA.
2
Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, Texas, USA.
3
Department of Chemistry, Rice University, Houston, Texas, USA.
4
Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas, USA.
5
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
6
Biology of Inflammation Center and the Michael E. DeBakey Virginia Center for Translational Research on Inflammatory Diseases, Houston, Texas, USA.

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.

PMID:
26437241
PMCID:
PMC4597310
DOI:
10.1038/ni.3292
[Indexed for MEDLINE]
Free PMC Article

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