Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, China.
Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Front Immunol. 2021 Jun 18;12:685400. doi: 10.3389/fimmu.2021.685400. eCollection 2021.
This study is to investigate the capacity of type 2 innate lymphoid cells (ILC2s) in regulating the Th2 type adaptive immune response of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The study enrolled healthy people, stable chronic obstructive pulmonary disease (COPD) patients, and AECOPD patients. Flow cytometry was used to detect Th2 and ILC2 cells in the peripheral blood. In addition, ILC2s from the peripheral blood of AECOPD patients were stimulated with PBS, IL-33, Jagged1, DAPT, IL-33+Jagged1, IL-33+DAPT, and IL-33+Jagged-1+DAP . The levels of cytokines in the culture supernatant were detected by ELISA and the culture supernatant was used to culture CD4 T cells. The mRNA and protein levels of Notch1, hes1, GATA3, RORα, and NF-κB of ILC2s were detected by real-time PCR and Western blot. The proportion of Th2 and ILC2s was significantly increased in the peripheral blood of AECOPD patients, alone with the increased , and mRNA levels. results showed that the mRNA and protein levels of Notch1, hes1, GATA3 and NF-κB were significantly increased after stimulation with Notch agonist, meanwhile, the level of type 2 cytokines were increased in the supernatant of cells stimulated with Notch agonist, and significantly promoted differentiation of Th2 cells Disruption of Notch pathway weakened GATA3 expression and cytokine production, and ultimately affected the differentiation of Th2 cells. In conclusion, our results suggest that ILC2s can promote Th2 cell differentiation in AECOPD activated Notch-GATA3 signal pathway.
本研究旨在探讨 2 型固有淋巴细胞（ILC2）在调节慢性阻塞性肺疾病急性加重（AECOPD）患者 Th2 型适应性免疫反应中的作用。该研究纳入了健康人、稳定期慢性阻塞性肺疾病（COPD）患者和 AECOPD 患者。采用流式细胞术检测外周血中的 Th2 和 ILC2 细胞。此外，用 PBS、IL-33、Jagged1、DAPT、IL-33+Jagged1、IL-33+DAPT 和 IL-33+Jagged1+DAPT 刺激 AECOPD 患者外周血中的 ILC2 细胞，通过 ELISA 检测培养上清液中细胞因子的水平，并将培养上清液用于培养 CD4+T 细胞。采用实时 PCR 和 Western blot 检测 ILC2 中 Notch1、hes1、GATA3、RORα 和 NF-κB 的 mRNA 和蛋白水平。AECOPD 患者外周血中 Th2 和 ILC2 比例明显升高，与 Notch1 基因及其下游基因 hes1、GATA3、RORα 和 NF-κB 的 mRNA 水平升高有关。结果表明，Notch 激动剂刺激后，ILC2 中 Notch1、hes1、GATA3 和 NF-κB 的 mRNA 和蛋白水平均明显升高，同时刺激 Notch 激动剂后细胞上清液中 2 型细胞因子水平升高，明显促进 Th2 细胞分化。Notch 通路的破坏减弱了 GATA3 的表达和细胞因子的产生，最终影响了 Th2 细胞的分化。综上所述，我们的研究结果表明，在 AECOPD 中，ILC2 通过激活 Notch-GATA3 信号通路促进 Th2 细胞分化。
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