Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, China.
Department of Clinical Laboratory, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
Mediators Inflamm. 2019 Jun 20;2019:3140183. doi: 10.1155/2019/3140183. eCollection 2019.
To investigate the effect of ILC2s on Th2-type adaptive immunity during the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the study enrolled healthy people, stable COPD patients, and AECOPD patients. Flow cytometry was used to detect Th1, Th2, and ILC2 in the peripheral blood and CD80 and MHC II levels on ILC2. The mRNA levels of , , and of ILC2s were detected by RT-PCR. In addition, ILC2s from the peripheral blood of AECOPD patients were cocultured with CD4 T cells from the peripheral blood of healthy controls. Cytokine levels in serum of the three groups and the in vitro coculture supernatants were measured by ELISA. Compared with the stable COPD group or the healthy control group, Th2 in the peripheral blood of AECOPD group increased dramatically, inducing an increase of Th2/Th1 ratio in AECOPD patients. Meanwhile, the level of IL-4 in the serum of this group was also increased. However, we also detected ILC2s in the peripheral blood of the AECOPD group and found that it was also increased, alone with the increased , , and mRNA levels. We also found that the CD80 and MHC II on ILC2 were significantly upregulated and the proportion of MHC II ILC2 cells was significantly positively correlated with the proportion of Th2 cells in AECOPD patients. To further demonstrate the effect of ILC2 on Th2 cells, we cocultured ILC2 with CD4 T cells in vitro, which also showed a significant increase of Th2 ratio as well as Th2-associated cytokines IL-4, IL-5, and IL-13. However, we found that this effect of ILC2s on Th2 cells could be inhibited by the addition of anti-MHC II. The Th2/Th1 balance shifts to Th2 in AECOPD. ILC2s may function as APC by the upregulation of MHC II and regulate adaptive immunity shift to Th2-type response in AECOPD.
为了研究 ILC2 在慢性阻塞性肺疾病（COPD）急性加重期（AECOPD）时对 Th2 型适应性免疫的影响，本研究纳入了健康人、稳定期 COPD 患者和 AECOPD 患者。采用流式细胞术检测外周血中的 Th1、Th2 和 ILC2 以及 ILC2 上的 CD80 和 MHC II 水平。通过 RT-PCR 检测 ILC2s 的 、 、 基因的 mRNA 水平。此外，将 AECOPD 患者外周血中的 ILC2 与健康对照者外周血中的 CD4 T 细胞共培养。通过 ELISA 检测三组血清细胞因子水平及体外共培养上清液中的细胞因子水平。与稳定期 COPD 组或健康对照组相比，AECOPD 组患者外周血中的 Th2 显著增加，导致 AECOPD 患者 Th2/Th1 比值增加。同时，该组血清中 IL-4 水平也升高。然而，我们还检测了 AECOPD 组外周血中的 ILC2，发现其也增加了，同时 、 、 基因的 mRNA 水平也增加了。我们还发现 ILC2 上的 CD80 和 MHC II 明显上调，AECOPD 患者中 MHC II ILC2 细胞的比例与 Th2 细胞的比例呈显著正相关。为了进一步证明 ILC2 对 Th2 细胞的作用，我们将 ILC2 与 CD4 T 细胞在体外共培养，结果也显示 Th2 比例以及 Th2 相关细胞因子 IL-4、IL-5 和 IL-13 明显增加。然而，我们发现 MHC II 的加入可以抑制 ILC2 对 Th2 细胞的这种作用。AECOPD 中 Th2/Th1 平衡向 Th2 转移。ILC2 可能通过 MHC II 的上调作为 APC 调节适应性免疫向 Th2 型反应转移。
