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. 2018 Jan;12(1):149-157.
doi: 10.1111/crj.12503. Epub 2016 Jun 22.

Critical roles of adenosine A2A receptor in regulating the balance of Treg/Th17 cells in allergic asthma

Linlin Wang  1 , Huanying Wan  2 , Wei Tang  2 , Yingmeng Ni  2 , Xiaoxia Hou  2 , Lina Pan  2 , Yuanlin Song  1   3   4 , Guochao Shi  2
Affiliations

Critical roles of adenosine A2A receptor in regulating the balance of Treg/Th17 cells in allergic asthma

Linlin Wang et al. Clin Respir J. 2018 Jan.

Abstract

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-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.

Keywords: A2A receptor; CGS21680; Th17 cells; Treg cells; asthma.

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