Search

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. [ABSTRACT FROM AUTHOR]

Background and Aims: 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 factorbeta 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. Conclusion: The histone deacetylase inhibitor TSA can regulate the balance of Th17/Treg in asthma by regulating the activity of histone deacetylase. [ABSTRACT FROM AUTHOR]