title: The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema.
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.
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: You
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas, USA.
authors.forename: Errol L G
authors.initials: EL
authors.lastname: Samuel
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas, USA.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Marcano
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas, USA.
authors.forename: William K A
authors.initials: WK
authors.lastname: Sikkema
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Tour
authors.affiliation: Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Antony
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas, USA.|Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, Texas, USA.|Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.|Biology of Inflammation Center and the Michael E. DeBakey Virginia Center for Translational Research on Inflammatory Diseases, Houston, Texas, USA.
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas, USA.|Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, Texas, USA.|Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.|Biology of Inflammation Center and the Michael E. DeBakey Virginia Center for Translational Research on Inflammatory Diseases, Houston, Texas, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004646:Emphysema / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D012907:Smoking / Q000009:adverse effects; D053260:Soot / Q000633:toxicity; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C548375:MIRN22 microRNA, human; D035683:MicroRNAs; C574876:Mirn22 microRNA, mouse; D016328:NF-kappa B; D012097:Repressor Proteins; D053260:Soot; D018808:Transcription Factor AP-1; C400300:HDAC4 protein, human; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases