摘要
AbstractBackground:The incidence of chronic obstructive pulmonary disease (COPD) complicated with invasive pulmonary aspergillosis (IPA) has increased in the last two decades. The mechanism underpinning susceptibility to and high mortality of COPD complicated with IPA is unclear, and the role of T helper cells 17 (Th17 cells) in the compound disease remains unknown. Therefore, this study aimed to assess the function of Th17 cells in COPD combined with IPA.Methods:COPD, IPA, and COPD+IPA mouse models were established in male wild type C57/BL6 mice. The amounts of Th17 cells and retinoic acid-related orphan receptors γt (RORγt) were tested by flow cytometry. Then, serum interleukin (IL)-17 and IL-23 levels were detected by enzyme-linked immunosorbent assay (ELISA) in the control, COPD, IPA and COPD+IPA groups. In addition, COPD+IPA was induced in IL-17 knockout (KO) mice, for determining the role of Th17 cells in COPD+IPA.Results:Compared with the COPD group, the COPD+IPA group showed higher amounts of blood RORγt ([35.09 ± 16.12]% vs. [17.92 ± 4.91]%, P = 0.02) and serum IL-17 (17.96 ± 9.59 pg/mL vs. 8.05 ± 4.44 pg/mL, P = 0.02), but blood ([5.18 ± 1.09]% vs. [4.15 ± 0.87]%, P= 0.28) and lung levels of Th17 cells ([1.98 ± 0.83]% vs. [2.03 ± 0.98]%, P= 0.91), lung levels of RORγt ([9.58 ± 6.93]% vs. [9.63 ± 5.98]%, P = 0.49) and serum IL-23 (51.55 ± 27.82 pg/mL vs. 68.70 ± 15.20 pg/mL, P = 0.15) showed no significant differences. Compared with the IPA group, the COPD+IPA group displayed lower amounts of blood ([5.18 ± 1.09]% vs. [9.21 ± 3.56]%, P = 0.01) and lung Th17 cells ([1.98 ± 0.83]% vs. [6.29 ± 1.11]%, P = 0.01) and serum IL-23 (51.55 ± 27.82 pg/mL vs. 154.90 ± 64.60 pg/mL, P = 0.01) and IL-17 (17.96 ± 9.59 pg/mL vs. 39.81 ± 22.37 pg/mL, P = 0.02), while comparable blood ([35.09 ± 16.12]% vs. [29.86 ± 15.42]%, P = 0.25) and lung levels of RORγt ([9.58 ± 6.93]% vs. [15.10 ± 2.95]%, P = 0.18) were found in these two groups. Finally, Aspergillus load in IL-17 KO COPD+IPA mice was almost 2 times that of COPD+IPA mice (1,851,687.69 ± 944,480.43 vs. 892,958.10 ± 686,808.80, t= 2.32, P = 0.02).Conclusion:These findings indicate that Th17 cells might be involved in the pathogenesis of COPD combined with IPA, with IL-17 likely playing an antifungal role.
机构地区
Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China,Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin 130041, China
出版日期
2021年03月21日(中国期刊网平台首次上网日期,不代表论文的发表时间)