ILC2 Cells Promote Th2 Cell Differentiation in AECOPD Through Activated Notch-GATA3 Signaling Pathway.
ILC2 Cells Promote Th2 Cell Differentiation in AECOPD Through Activated Notch-GATA3 Signaling Pathway.
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ILC2细胞通过激活Notch-GATA3信号通路促进AECOPD中Th2细胞分化
DOI：
10.3389/fimmu.2021.685400
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发表时间：
2021
影响因子：
7.3
通讯作者：
Ding J
中科院分区：
文献类型：
--
作者：
Jiang M;Cai R;Wang J;Li Z;Xu D;Jing J;Zhang F;Li F;Ding J
本研究旨在探讨2型先天性淋巴细胞（ILC 2）对慢性阻塞性肺疾病急性加重期（AECOPD）患者Th 2型适应性免疫应答的调节作用。该研究招募了健康人，稳定的慢性阻塞性肺疾病（COPD）患者和AECOPD患者。流式细胞术检测外周血Th 2和ILC 2细胞。另外，用PBS、IL-33、Jagged 1、DAPT、IL-33 + Jagged 1、IL-33+DAPT和IL-33+Jagged-1+DAP体外刺激来自AECOPD患者外周血的ILC 2。ELISA法检测培养上清中细胞因子的水平，并将培养上清用于培养CD 4 + T细胞。实时定量PCR和Western blot检测ILC 2中Notch 1、hes 1、GATA 3、RORα和NF-κB的mRNA和蛋白水平。AECOPD患者外周血中Th 2和ILC 2s的比例显著增加，Notch 1、hes 1和GATA 3 mRNA水平升高。体外实验结果显示，Notch激动剂刺激后，Notch 1、hes 1、GATA 3和NF-κB的mRNA和蛋白水平均显著升高，同时Notch激动剂刺激后细胞上清液中2型细胞因子水平升高，并显著促进Th 2细胞的体外分化。Notch信号通路的阻断可减弱GATA 3的表达和细胞因子的产生，最终影响Th 2细胞的分化。结论：ILC 2s可通过激活Notch-GATA 3信号通路促进AECOPD患者Th 2细胞分化。
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 in vitro. 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 Notch1, hes1, and GATA3 mRNA levels. In vitro 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 in vitro. 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 via activated Notch-GATA3 signal pathway.
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