title: Critical roles of adenosine A2A receptor in regulating the balance of Treg/Th17 cells in allergic asthma.
abstract: BACKGROUND
  Deficiency of Treg cells and hyperactivity of Th17 cells together are involved in the immunological pathogenesis of asthma. The adenosine A2A receptor (A2AR) plays a critical role in the increased Foxp3 expression of Treg cells and the decreased Th17 generation.
  
  
  OBJECTIVE
  The study aimed to investigate A2AR expression in peripheral blood and its regulatory effect on balance of Treg/Th17 cells in asthma.
  
  
  METHODS
  Thirty-one patients with chronic persistent asthma were recruited and divided into 18 intermittent to mild asthma patients, 13 moderate to severe asthma patients. A2AR, Foxp3, and ROR-γt mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were measured by quantitative polymerase chain reaction (qPCR). TGF-β, IL-17, and IgE in plasma were detected with enzyme-linked immunosorbent assay (ELISA). Forty-two BALB/c mice were randomly, equally assigned to control group, ovalbumin (OVA) group and OVA + CGS (CGS21680, A2AR agonist) group. The infiltration of lung inflammation cells were evaluated by HE, A2AR, Foxp3, and ROR-γt mRNA in lung tissues measured by qPCR, TGF-β, IL-17, and IgE in plasma measured with ELISA, and IL-17 and TGF-β protein in lung tissues analyzed with immunohistochemical.
  
  
  RESULTS
  Our results showed that expression A2AR mRNA in PBMCs was associated with asthma severity. Foxp3 mRNA, TGF-β, and FEV1%pred positively correlated with A2AR mRNA in asthma. ROR-γt mRNA and IL-17 negatively correlated with A2AR mRNA in asthma. CGS could promote Foxp3 mRNA expression, TGF-β, and improve lung function while inhibit ROR-γt mRNA expression, IL-17, and the infiltration of lung inflammation cells.
  
  
  CONCLUSIONS
  A2AR could regulate the balance of Treg/Th17 cells in asthma.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, 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, 200025, 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, 200025, 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, 200025, 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, 200025, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Shanghai Public Health Clinical Center, Shanghai, 201508, China.|Department of Pulmonary Medicine, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, 201700, China.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Guochao
authors.initials: G
authors.lastname: Shi
mesh_terms: D000328:Adult; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear; D008297:Male; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D043705:Receptor, Adenosine A2A / Q000096:biosynthesis / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A
keywords: A2A receptor; CGS21680; Th17 cells; Treg cells; asthma