ILC2s Induce Adaptive Th2-Type Immunity in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
ILC2s Induce Adaptive Th2-Type Immunity in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
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ILC2 在慢性阻塞性肺疾病急性加重中诱导适应性 Th2 型免疫
DOI：
10.1155/2019/3140183
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发表时间：
2019-01-01
影响因子：
4.6
通讯作者：
Ding, Jianbing
中科院分区：
文献类型：
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作者：
Jiang, Min;Liu, Huifang;Ding, Jianbing
为了研究ILC2s对慢性阻塞性肺疾病（AECOPD）急性加重期th2型适应性免疫的影响，本研究招募了健康人群、稳定期COPD患者和AECOPD患者。流式细胞术检测外周血中Th1、Th2、ILC2及ILC2上CD80、MHC II水平。RT-PCR检测ILC2s中GATA3、rora、CRTH2 mRNA表达水平。此外，将AECOPD患者外周血中的ILC2s与健康对照组外周血中的CD4+ T细胞共培养。采用ELISA法检测各组血清及体外共培养上清细胞因子水平。与稳定期COPD组或健康对照组相比，AECOPD组外周血Th2显著升高，导致AECOPD患者Th2/Th1比值升高。同时，血清中IL-4水平也升高。然而，我们也检测了AECOPD组外周血中的ILC2s，发现ILC2s也升高，仅GATA3、rora和CRTH2 mRNA水平升高。我们还发现AECOPD患者ILC2上的CD80和MHC II显著上调，MHC II+ ILC2细胞比例与Th2细胞比例显著正相关。为了进一步证明ILC2对Th2细胞的作用，我们在体外将ILC2与CD4+ T细胞共培养，结果也显示出Th2比例以及Th2相关细胞因子IL-4、IL-5和IL-13的显著增加。然而，我们发现ILC2s对Th2细胞的这种作用可以通过添加抗mhc II来抑制。在AECOPD中，Th2/Th1平衡转向Th2。ILC2s可能通过上调MHC II发挥APC的作用，调节AECOPD的适应性免疫向th2型反应的转变。
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 GATA3, RORα, and CRTH2 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 GATA3, RORα, and CRTH2 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.