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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Disease Models, Animal
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Emphysema / etiology*
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Emphysema / immunology
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Emphysema / metabolism
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Histone Deacetylases / metabolism
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Humans
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Lung / immunology
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Lung / metabolism
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Lung / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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MicroRNAs / genetics*
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MicroRNAs / metabolism*
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NF-kappa B / metabolism
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Repressor Proteins / antagonists & inhibitors*
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Smoking / adverse effects
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Soot / toxicity
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Th17 Cells / immunology*
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Th17 Cells / metabolism
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Transcription Factor AP-1 / metabolism
Substances
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MIRN22 microRNA, human
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MicroRNAs
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Mirn22 microRNA, mouse
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NF-kappa B
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Repressor Proteins
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Soot
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Transcription Factor AP-1
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HDAC4 protein, human
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Hdac5 protein, mouse
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Histone Deacetylases