Critical roles of adenosine A2A receptor in regulating the balance of Treg/Th17cells in allergic asthma.

Introduction: 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-gamma t mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were measured by quantitative polymerase chain reaction (qPCR). TGF-beta, 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-gamma t mRNA in lung tissues measured by qPCR, TGF-beta, IL-17, and IgE in plasma measured with ELISA, and IL-17 and TGF-beta 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-beta, and FEV1%pred positively correlated with A2AR mRNA in asthma. ROR-gamma t mRNA and IL-17 negatively correlated with A2AR mRNA in asthma. CGS could promote Foxp3 mRNA expression, TGF-beta, and improve lung function while inhibit ROR-gamma t mRNA expression, IL-17, and the infiltration of lung inflammation cells. Conclusion: A2AR could regulate the balance of Treg/Th17 cells in asthma.