Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS).

Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).

Solar ultraviolet B radiation promotes α-MSH secretion to attenuate the function of ILC2s via the pituitary-lung axis.

The immunomodulatory effects of ultraviolet B (UVB) radiation in human diseases have been described. Whether type 2 lung inflammation is directly affected by solar ultraviolet (UV) radiation is not fully understood. Here, we show a possible negative correlation between solar UVB radiation and asthmatic inflammation in humans and mice. UVB exposure to the eyes induces hypothalamus-pituitary activation and α-melanocyte-stimulating hormone (α-MSH) accumulation in the serum to suppress allergic airway inflammation by targeting group 2 innate lymphoid cells (ILC2) through the MC5R receptor in mice. The α-MSH/MC5R interaction limits ILC2 function through attenuation of JAK/STAT and NF-κB signaling. Consistently, we observe that the plasma α-MSH concentration is negatively correlated with the number and function of ILC2s in the peripheral blood mononuclear cells (PBMC) of patients with asthma. We provide insights into how solar UVB radiation-driven neuroendocrine α-MSH restricts ILC2-mediated lung inflammation and offer a possible strategy for controlling allergic diseases.

PTRF-IL33-ZBP1 signaling mediating macrophage necroptosis contributes to HDM-induced airway inflammation.

Polymerase 1 and transcript release factor (PTRF, encoding by Cavin-1) regulates interleukin 33 (IL-33) release, which is implicated in asthma development. Z-DNA binding protein 1 (ZBP1)-sensing Z-RNAs induces necroptosis which causes inflammatory diseases. House dust mite (HDM) is the major source of allergen in house dust and is strongly associated with the development of asthma. Whether PTRF via IL-33 and ZBP1 mediates HDM-induced macrophage necroptosis and airway inflammation remains unclear. Here, we found that deficiency of PTRF could reduce lung IL-33, ZBP1, phosphor-receptor-interacting protein kinase 3 (p-RIPK3), and phosphor-mixed lineage kinase domain-like (p-MLKL) (necroptosis executioner), and airway inflammation in an HDM-induced asthma mouse model. In HDM-treated macrophages, ZBP1, p-RIPK3, and p-MLKL levels were markedly increased, and these changes were reversed by deletion of Cavin-1. Deletion of Il33 also reduced expression of ZBP1, p-RIPK3, and p-MLKL in HDM-challenged lungs. Moreover, IL-33 synergizing with HDM boosted expression of ZBP1, p-RIPK3, and p-MLKL in macrophages. In bronchial epithelial cells rather than macrophages and vascular endothelial cells, PTRF positively regulates IL-33 expression. Therefore, we conclude that PTRF mediates HDM-induced macrophage ZBP1/necroptosis and airway inflammation, and this effect could be boosted by bronchial epithelial cell-derived IL-33. Our findings suggest that PTRF-IL33-ZBP1 signaling pathway might be a promising target for dampening airway inflammation.

Diagnostic Efficacy of T-SPOT.TB for Active Tuberculosis in Adult: A Retrospective Study.

Purpose: To explore the diagnostic efficacy and optimal diagnosis threshold of T-SPOT.TB for active tuberculosis in adults and to evaluate the influential factors for T-SPOT.TB results. Patients and Methods: A retrospective study of 1193 adult inpatients from April 2015 to March 2018 in Ruijin Hospital was conducted. All included patients underwent T-SPOT.TB assay, and were divided into two groups, active tuberculosis (ATB) and non-active tuberculosis (non-ATB) groups. Their demographic data, underlying diseases, personal history and laboratory findings were collected to calculate the diagnostic efficacy at different diagnosis thresholds and analyze the impact factors. Symptoms and imaging features of ATB patients were recorded and analyzed. Results: A total of 114 ATB patients and 1079 non-ATB patients were included in the study, and ATB patients had a higher level of T-SPOT.TB than the non-ATB group. Sensitivity and specificity of T-SPOT.TB for diagnosing ATB are 78.95% and 68.58% as the threshold at 6sfu. In the diagnosis accordance curves, ESAT-6, CFP-10, and max (ESAT-6 or CFP-10) reached the plateau at 40sfu, while sum (ESAT-6 and CFP-10) reached the plateau at 70sfu. Multivariate logistic regression analysis showed that obsolescent tuberculosis (p=0.001), smoking history(p=0.005), diabetes(p=0.035) and advanced age (≥65 years old) (p=0.031) were risk factors for false-positive result of T-SPOT.TB. In terms of imaging features, logistic regression analysis suggested that the thin-wall cavitary lesion was the only feature associated with the result of T-SPOT.TB. Conclusion: As for using T-SPOT.TB test to diagnose active tuberculosis, increased threshold could significantly elevate the diagnosis accordance. And we suggest that the threshold of T-SPOT.TB could be increased to 40sfu for diagnosing ATB. Attention should be paid when diagnose ATB in population with obsolescent tuberculosis, smoking history, diabetes and advanced age, for the risk of false-positive.

Clinical and imaging findings of patients diagnosed with adenovirus-positive pneumonia during 2015-2019 in Shanghai, China.

BACKGROUND: This study was to describe the clinical characteristics, chest CT image findings, and potential role of T cells immunity in adenovirus positive pneumonia. METHODS: In this retrospective study, medical records of 53 adult Adv+ patients who were admitted to the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from May 2015 to August 2019 were included. The presence of adenovirus and other respiratory viruses was detected using polymerase chain reaction of throat swabs samples. Clinical features and chest computed tomography (CT) findings were compared between patients with Adv+ pneumonia and Adv+ non-pneumonia. RESULTS: The top 3 most commonly occurring symptoms in Adv+ pneumonia patients were fever (66.7%), cough (63.3%), and tachypnea (16.7%). Patients with Adv+ pneumonia showed significantly higher rates of cough and fever and longer duration of hospitalization than patients with Adv+ non-pneumonia. In the Adv+ pneumonia group, consolidation (73.3%) was the most common imaging finding on chest CT scan, and the likelihood of involvement of bilateral lobes (60%) was high. Classical conspicuous consolidation with surrounding ground-glass opacity was observed in 5 (16.6%) patients with Adv+ pneumonia. Patients with Adv+ pneumonia showed a higher inhibition of T-cell immunity than did patients with Adv+ non-pneumonia, and counts of CD3+, CD4+, and CD8+ T-cells may predict the presence of pneumonia in Adv+ patients. DISCUSSION: With regard to Adv+ pneumonia, the most frequent symptoms were cough and fever, and the most common CT pattern was consolidation; classical CT findings such as consolidation with surrounding ground-glass opacity could also be observed. Furthermore, our data indicated the incidence of abrogated cellular immunity in patients with Adv+ pneumonia.

The effect of short-chain fatty acids on M2 macrophages polarization in vitro and in vivo.

Alternatively activated macrophages (M2 polarization) play an important role in asthma. Short-chain fatty acids (SCFAs) possessed immune-regulatory functions, but their effects on M2 polarization of alveolar macrophages and its underlying mechanisms are still unclear. In our study, murine alveolar macrophage MH-S cell line and human monocyte-derived macrophages were used to polarize to M2 subset with interleukin-4 (IL-4) treatment. The underlying mechanisms involved were investigated using molecule inhibitors/agonists. In vivo, female C57BL/6 mice were divided into five groups: CON group, ovalbumin (OVA) asthma group, OVA+Acetate group, OVA+Butyrate group, and OVA+Propionate group. Mice were fed with or without SCFAs (Acetate, Butyrate, Propionate) in drinking water for 20 days before developing OVA-induced asthma model. In MH-S, SCFAs inhibited IL-4-incuced protein or mRNA expressions of M2-associated genes in a dose-dependent manner. G-protein-coupled receptor 43 (GPR43) agonist 4-CMTB and histone deacetylase (HDAC) inhibitor (trichostatin A, TSA), but not GPR41 agonist AR420626 could inhibit the protein or mRNA expressions M2-associated genes. 4-CMTB, but not TSA, had no synergistic role in the inhibitory effect of SCFAs on M2 polarization. In vivo study indicated Butyrate and Propionate, but not Acetate, attenuated OVA-induced M2 polarization in the lung and airway inflammation. We also found the inhibitory effect of SCFAs on M2 polarization in human-derived macrophages. Therefore, SCFAs inhibited M2 polarization in MH-S likely through GPR43 activation and/or HDAC inhibition. Butyrate and Propionate but not Acetate could inhibit M2 polarization and airway inflammation in asthma model. SCFAs also abrogated M2 polarization in human-derived macrophages.

Insulin signaling establishes a developmental trajectory of adipose regulatory T cells.

Systematic characterizations of adipose regulatory T (Treg) cell subsets and their phenotypes remain uncommon. Using single-cell ATAC-sequencing and paired single-cell RNA and T cell receptor (TCR) sequencing to map mouse adipose Treg cells, we identified CD73hiST2lo and CD73loST2hi subsets with distinct clonal expansion patterns. Analysis of TCR-sharing data implied a state transition between CD73hiST2lo and CD73loST2hi subsets. Mechanistically, we revealed that insulin signaling occurs through a HIF-1α-Med23-PPAR-γ axis to drive the transition of CD73hiST2lo into a CD73loST2hi adipose Treg cell subset. Treg cells deficient in insulin receptor, HIF-1α or Med23 have decreased PPAR-γ expression that in turn promotes accumulation of CD73hiST2lo adipose Treg cells and physiological adenosine production to activate beige fat biogenesis. We therefore unveiled a developmental trajectory of adipose Treg cells and its dependence on insulin signaling. Our findings have implications for understanding the dynamics of adipose Treg cell subsets in aged and obese contexts.

Preclinical efficacy and clinical safety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) turn out to be a promising source of cell-free therapy. Here, we investigated the biodistribution and effect of nebulized human adipose-derived MSC-EVs (haMSC-EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC-EVs in healthy volunteers. DiR-labelled haMSC-EVs were used to explore the distribution of nebulized haMSC-EVs in the murine model. Pseudomonas aeruginosa-induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL-6, TNF-α and IL-10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC-EVs through the nebulized route. Twenty-four healthy volunteers were involved and received the haMSC-EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, NCT04313647). Nebulizing haMSC-EVs improved survival rate to 80% at 96 h in P. aeruginosa-induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC-EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC-EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC-EVs in lung injury diseases.

Insights into gut microbiome and its functional pathways in asthma patients through high-throughput sequencing.

Aim: To describe gut microbiome and functional genes of asthma. Patients & methods: Fecal microbiome in controls, asthma patients with and without inhaled corticosteroid (ICS) treatment was determined. Results: Patients with ICS had lower abundance of Alloprevotella, unclassified_f_Lachnospiraceae and Lachnospiraceae_NC2004_group, higher abundance of Sutterella and Sphingomonas than patients without ICS. In all the asthma patients, there are microbial differences in aging distribution, different gender and different asthmatic phenotypes. Asthma patients without ICS treatment had more microbial genes related to geraniol degradation, ethylbenzene degradation and bladder cancer than controls; 15 pathways showed significant difference between asthma patients with and without ICS treatment. Conclusion: We found gut dysbiosis in asthma and different functional pathways associated with both asthma and ICS.

How does comorbid bronchiectasis affect asthmatic patients? A meta-analysis.

OBJECTIVE: Asthma and bronchiectasis are known to be two distinct diseases with different etiology, pathophysiology, management, and prognosis. However, a high prevalence of bronchiectasis has been reported in patients with severe asthma. Thus, it is of great importance to identify the impact of bronchiectasis on asthmatic patients. DATA SOURCES: Databases including PubMed, Embase, Cochrane, Web of Science were searched comprehensively to identify relevant human clinical studies published until February 2020. STUDY SELECTIONS: Two investigators (Gelei Lan and Guochao Shi) independently obtained the potentially eligible articles based on their titles and abstracts. When opinions differed between the investigators, discussions were made to reach an agreement. The authors of the included studies were contacted for inquiry when necessary. RESULTS: Six observational studies with 1004 patients were included in the meta-analysis. The mean prevalence of bronchiectasis in patients with asthma was 35.2% (ranging from 2.2% to 47%). Asthmatic patients with bronchiectasis were older, had a longer disease duration, exhibited greater severity, and showed more frequent exacerbations and hospitalization, and poorer lung function, compared with the patients without bronchiectasis. CONCLUSION: Despite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of comorbid bronchiectasis on asthmatic patients. Thus, coexistence of bronchiectasis should be considered a clinical phenotype of asthma, which may have associations with exacerbation and hospitalization.

Double lung transplantation for Sjögren's syndrome-related interstitial lung disease: a case report and review of literature.

In this study, we present a case of 65-year-old male patient with suspected Sjögren's syndrome-related interstitial lung disease (SS-ILD) with initial symptoms of limb edema and acute respiratory failure. He was treated with immunosuppressor, respiratory support, dialysis, immunomodulatory, and anti-inflammatory medications. However, no significant response was shown to anti-fibrotic treatments and his respiratory function deteriorated. Double lung transplantation was thus indicated considering the irreversible interstitial changes in both lungs. The surgical procedure was complicated, and the role of enhanced recovery after surgery (ERAS) for this critical patient was discussed. The patient experienced hemorrhage, pulmonary infection, and peripheral neuropathy after surgery, but he was cured by the multidisciplinary team. He had a satisfactory quality of life at 1-year follow-up. This case report describes the details of double lung transplantation in a patient with advanced SS-ILD. Important considerations include the indications for and timing of transplantation, the effects of long-term immunosuppression on wound healing, and extrapulmonary organ dysfunction. Based on a review of the published literature and a consideration of the short-term outcomes, lung transplantation for this individual with an autoimmune disease appears to be safe and feasible. SS-ILD should not be a contraindication to transplantation; however, patients with advanced pulmonary involvement should be carefully selected after a multidisciplinary evaluation. More long-term follow-up and further comparative studies are needed in the future.

The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.

The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear. Here, we identify the ubiquitin-specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3. USP44 interacts with and stabilizes FOXP3 by removing K48-linked ubiquitin modifications. Notably, TGF-ß induces USP44 expression during iTreg differentiation. USP44 co-operates with USP7 to stabilize and deubiquitinate FOXP3. Tregs genetically lacking USP44 are less effective than their wild-type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer. These findings suggest that USP44 plays an important role in the post-translational regulation of Treg function and is thus a potential therapeutic target for tolerance-breaking anti-cancer immunotherapy.

Indoor PM2.5, tobacco smoking and chronic lung diseases: A narrative review.

The lung is one of the most important organs exposed to environmental agents. People spend approximately 90% of their time indoors, and risks to health may thus be greater from exposure to poor air quality indoors than outdoors. Multiple indoor pollutants have been linked to chronic respiratory diseases. Environmental tobacco smoke (ETS) is known as an important source of multiple pollutants, especially in indoor environments. Indoor PM2.5 (particulate matter with aerodynamic diameter < 2.5 µm) was reported to be the most reliable marker of the presence of tobacco smoke. Recent studies have demonstrated that PM2.5 is closely correlated with chronic lung diseases. In this paper, we reviewed the relationship of tobacco smoking and indoor PM2.5 and the mechanism that underpin the link of tobacco smoke, indoor PM2.5 and chronic lung diseases.

Smoking and microbiome in oral, airway, gut and some systemic diseases.

The human microbiome harbors a diverse array of microbes which establishes a mutually beneficial relation with the host in healthy conditions, however, the dynamic homeostasis is influenced by both host and environmental factors. Smoking contributes to modifications of the oral, lung and gut microbiome, leading to various diseases, such as periodontitis, asthma, chronic obstructive pulmonary disease, Crohn's disease, ulcerative colitis and cancers. However, the exact causal relationship between smoking and microbiome alteration remains to be further explored.

Biomimetic synthesis of Ag-coated glasswing butterfly arrays as ultra-sensitive SERS substrates for efficient trace detection of pesticides.

In this work, we report a biomimetic synthesis route of 3D Ag nanofilm/glasswing butterfly wing hybrids (Ag-G.b.) by magnetron sputtering technology. The 3D surface-enhanced Raman scattering (SERS) substrate is fabricated from an original chitin-based nanostructure, which serves as a bio-scaffold for Ag nanofilms to be coated on. The novel crisscrossing plate-like nanostructures of 3D Ag-G.b. nanohybrids with thick Ag nanofilms provide a substantial contribution to SERS enhancement. Measuring the SERS performance with crystal violet (CV), the Ag-G.b. nanohybrids with the sputtering time of 20 min (Ag-G.b.-20) shows the highest enhancement performance with an enhancement factor (EF) of up to 2.96 × 107. The limit of detection (LOD) for CV was as low as 10-11 M, demonstrating the ultrahigh sensitivity of the Ag-G.b.-20 substrate. In addition, the Ag-G.b.-20 substrate has an outstanding reproducibility across the entire area with the maximum value of relative standard deviation (RSD) of less than 10.78%. The nanohybrids also exhibit a long-term stability regarding Raman enhancement, as suggested by a duration stability test over a period of 60 days. Importantly, the high-performance Ag-G.b.-20 substrate is further applied as an ultra-sensitive SERS platform for the trace detection of acephate, showing its great potential application in biochemical sensing and food security.

Intratracheal administration of adipose derived mesenchymal stem cells alleviates chronic asthma in a mouse model.

BACKGROUND: Adipose-derived mesenchymal stem cell (ASCs) exerts immunomodulatory roles in asthma. However, the underlying mechanism remains unclear. The present study aimed to explore the effects and mechanisms of ASCs on chronic asthma using an ovalbumin (OVA)-sensitized asthmatic mouse model. METHODS: Murine ASCs (mASCs) were isolated from male Balb/c mice and identified by the expression of surface markers using flow cytometry. The OVA-sensitized asthmatic mouse model was established and then animals were treated with the mASCs through intratracheal delivery. The therapy effects were assessed by measuring airway responsiveness, performing immuohistochemical analysis, and examining bronchoalveolar lavage fluid (BALF). Additionally, the expression of inflammatory cytokines and lgE was detected by CHIP and ELISA, respectively. The mRNA levels of serum indices were detected using qRT-PCR. RESULTS: The mASCs grew by adherence with fibroblast-like morphology, and showed the positive expression of CD90, CD44, and CD29 as well as the negative expression of CD45 and CD34, indicating that the mASCs were successfully isolated. Administering mASCs to asthmatic model animals through intratracheal delivery reduced airway responsiveness, the number of lymphocytes (P < 0.01) and the expression of lgE (P < 0.01), IL-1ß (P < 0.05), IL-4 (P < 0.001), and IL-17F (P < 0.001), as well as increased the serum levels of IL-10 and Foxp3, and the percentage of CD4 + CD25 + Foxp3+ Tregs in the spleen, and reduced the expression of IL-17 (P < 0.05) and RORγ. CONCLUSIONS: Intratracheal administration of mASCs alleviated airway inflammation, improved airway remodeling, and relieved airway hyperresponsiveness in an OVA-sensitized asthma model, which might be associated with the restoration of Th1/Th2 cell balance by mASCs.

Hedgehog signaling regulates the expression levels of inflammatory mediators in cigarette­induced airway inflammation.

Chronic obstructive pulmonary disease (COPD) is a persistent airway inflammation influenced by cigarette smoke. Previous studies have reported that Hedgehog (Hh) signaling is aberrantly activated by cigarette smoke and dysregulated in COPD. The present study explored the role of the Hh signaling pathway on the expression levels of certain inflammatory mediators in cigarette­induced airway inflammation. Herein, a total of three A549 cell populations were generated: The A0 group as control cells, the A1 group cells treated with nicotine at a concentration of 10 µM for 12, 24 and 48 h, and the A2 group cultured simultaneously with nicotine and cyclopamine for the same duration. The total concentrations of the inflammatory mediators interleukin­6 (IL­6), IL­8 and tumor necrosis factor (TNF)­α, and an anti­inflammatory cytokine, IL­10, were assessed in all of the cells by ELISA and western blotting. The protein levels of sonic hedgehog (Shh), glioma­associated oncoprotein 1 (Gli1) and Smoothened (Smo) in nicotine­induced Hh signaling were also detected. The results indicated that A549 had increased levels of IL­6, IL­8 and TNF­α when cultured with nicotine when compared with the control cells. By contrast, the expression levels of these inflammatory mediators decreased with varying degrees when treated with cyclopamine that blocked the Hh signaling pathway. The IL­10 expression levels exhibited the reverse. The expressions of the Shh, Gli1 and Smo proteins were higher in the A1 group when compared with the control and decreased with cyclpoamine treatment. In conclusion, the Hh signaling pathway may partly have an impact on cigarette­induced airway inflammation via the regulation of inflammatory mediators. Thus, blocking Hh signaling and diminishing the airway inflammation reaction may serve as a potential therapy for COPD.

Critical roles of adenosine A2A receptor in regulating the balance of Treg/Th17 cells 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-γt mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were measured by quantitative polymerase chain reaction (qPCR). TGF-ß, 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-ß, IL-17, and IgE in plasma measured with ELISA, and IL-17 and TGF-ß 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-ß, 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-ß, 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.