title: Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma.
abstract: OBJECTIVE
  The aim of this study is to investigate the expression pattern of histone deacetylase 9 in peripheral blood of patients with allergic asthma and its regulatory effect on the balance of Th17/Treg cells involved in the pathogenesis of asthma.
  
  
  METHODS
  flap-Ub promoter-GFP-WRE vector was used to construct the Jurkat-HA-FOXP3 cell line. After histone deacetylase inhibitor-trichostatin A (TSA) treatment, FOXP3 and RORγt expression were detected by real-time-polymerase chain reaction (RT-PCR). BALB/c mice were randomly assigned to control group, TSA treatment and the asthma group. Serum Immunoglobulin E (IgE) was detected with enzyme-linked immunosorbent assay (ELISA), airway inflammation in lung tissue evaluated by haematoxylin/eosin staining, bronchoalveolar lavage fluid (BALF) cell number and differential counted, interleukin (IL)-17A and TGF-β concentrations in BALF measured with ELISA, and expression of RORγt and FOXP3 messenger RNA (mRNA)measured by RT-PCR. Forty-seven patients with asthma were recruited and assigned to intermittent, mild and moderate-severe group. GATA3, IL-4, histone deacetylases (HDAC) 9 mRNA expression level were measured by RT-PCR.
  
  
  RESULTS
  After TSA treatment, FOXP3 mRNA level was upregulated, while RORγt mRNA level was downregulated. FOXP3 protein level was also upregulated by TSA. In vivo, TSA treatment can inhibit IL-17 but promote transforming growth factor-beta production in the BALF of asthma mice, and inhibited the expression of Th17 cells and RORγt mRNA in lung; also can promote Foxp3 mRNA expression. GATA3, IL-4 mRNA expression levels were upregulated in patients with asthma than the healthy control. HDAC9 mRNA expression level was associated with the severity of disease.
  
  
  CONCLUSIONS
  The histone deacetylase inhibitor TSA can regulate the balance of Th17/Treg in asthma by regulating the activity of histone deacetylase.
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huanying
authors.initials: H
authors.lastname: Wan
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Ai
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yingmeng
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Guochao
authors.initials: G
authors.lastname: Shi
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics; D011897:Random Allocation; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D012097:Repressor Proteins; C012589:trichostatin A; C486544:HDAC9 protein, human; D006655:Histone Deacetylases
keywords: Th17; Treg; asthma; histone deacetylase inhibitor