Type 2 innate lymphoid cells participate in IL-33-stimulated Th2-associated immune response in chronic obstructive pulmonary disease
Type 2 innate lymphoid cells participate in IL-33-stimulated Th2-associated immune response in chronic obstructive pulmonary disease
复制标题
2型先天淋巴细胞参与慢性阻塞性肺疾病中IL-33刺激的Th2相关免疫反应
DOI：
10.3892/etm.2019.7924
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发表时间：
2019-10-01
影响因子：
2.7
通讯作者：
Ding, Jianbing
中科院分区：
文献类型：
--
作者：
Jiang, Min;Tao, Simin;Ding, Jianbing
本研究的目的是探讨 2 型先天淋巴细胞 (ILC2) 和白细胞介素 33 (IL-33) 在慢性阻塞性肺疾病 (COPD) 中的作用。从健康对照者和 COPD 患者中分离血清和外周血单核细胞 (PBMC)。体外用IL-33或中和ST2抗体+IL-33刺激来自COPD患者外周血的ILC2细胞。使用 Cell Counting Kit-8 测定法评估细胞活力。采用ELISA法检测血清IL-33以及培养上清液中IL-4、IL-5、IL-6、IL-13和可溶性ST2（sST2）的水平。通过流式细胞术测量ILC2细胞的百分比。采用逆转录定量PCR法检测GATA结合蛋白3（GATA3）、RAR相关孤儿受体（ROR）α、ST2和前列腺素D2受体2（CRTH2）的mRNA表达水平。研究发现，COPD患者外周血中IL-33、IL-5、IL-6和IL-13显着升高。 COPD患者外周血ILC2比例显着升高，RORA、CRTH2表达升高。 ST2(+)ILC2细胞比例显着增加。 IL-33体外刺激48 h后，谱系(-)CD45(+)CD127(+)CRTH2(+)细胞比例达到最大。此外，ILC2细胞的活力、RORA、GATA3、ST2和CRTH2 mRNA的表达水平以及细胞因子IL-4、IL-6、IL-5、IL-13和sST2的表达水平显着增加。这些效应通过抗ST2治疗消除。总之，COPD患者血清中IL-33表达上调，PBMCs中ILC2的比例增加。 IL-33可能促进ILC2细胞增殖并分泌2型T辅助细胞细胞因子参与COPD的免疫反应。
The aim of the present study was to investigate the roles of type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) in chronic obstructive pulmonary disease (COPD). Serum and peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and COPD patients. ILC2 cells from the peripheral blood of COPD patients were stimulated with IL-33 or neutralizing ST2 antibody+IL-33 in vitro. The cell viability was assessed using a Cell Counting Kit-8 assay. ELISA was used to detect serum IL-33 and the levels of IL-4, IL-5, IL-6, IL-13 and soluble ST2 (sST2) in the culture supernatant. The percentage of ILC2 cells was measured by flow cytometry. The mRNA expression levels of GATA binding protein 3 (GATA3), RAR-related orphan receptor (ROR)alpha, ST2 and prostaglandin D2 receptor 2 (CRTH2) were detected by reverse transcription-quantitative PCR. It was revealed that IL-33, IL-5, IL-6 and IL-13 were significantly elevated in peripheral blood of patients with COPD. The proportion of ILC2s in peripheral blood of COPD patients was significantly increased, and the expression of RORA and CRTH2 was increased. The proportion of ST2(+) ILC2 cells was significantly increased. After 48 h of IL-33 stimulation in vitro, the ratio of linage(-)CD45(+)CD127(+)CRTH2(+) cells reached a maximum. In addition, the viability of ILC2 cells, the expression levels of RORA, GATA3, ST2 and CRTH2 mRNA and the cytokines IL-4, IL-6, IL-5, IL-13 and sST2 were significantly increased. These effects were abrogated by treatment with anti-ST2. In conclusion, IL-33 is upregulated in the serum of patients with COPD and the proportion of ILC2s among the PBMCs is increased. IL-33 may promote the proliferation of ILC2 cells and secrete type 2 T-helper cell cytokines to participate in the immune response in COPD.