Open AccessCritical roles of adenosine A2A receptor in regulating the balance of Treg/Th17 cells in allergic asthma
Author(s) -
Wang Linlin,
Wan Huanying,
Tang Wei,
Ni Yingmeng,
Hou Xiaoxia,
Pan Lina,
Song Yuanlin,
Shi Guochao
Publication year - 2018
Publication title -
the clinical respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.789
H-Index - 33
eISSN - 1752-699X
pISSN - 1752-6981
DOI - 10.1111/crj.12503
Subject(s) - foxp3 , medicine , rar related orphan receptor gamma , immunology , ovalbumin , asthma , immunoglobulin e , pathogenesis , peripheral blood mononuclear cell , adenosine a2a receptor , receptor , immune system , adenosine receptor , agonist , biology , antibody , biochemistry , in vitro
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. Conclusion A2AR could regulate the balance of Treg/Th17 cells in asthma.