| 孙凤飞,马东海,史宏磊,林旻旻,刘 晶.糖皮质激素下调JAK/STAT抑制嗜酸粒细胞哮喘[J].,2022,(21):4117-4124 |
| 糖皮质激素下调JAK/STAT抑制嗜酸粒细胞哮喘 |
| Type 2 Innate Lymphoid Cells Activity are Inhibited by glucocorticoids via Down-regulation of JAK/STAT in Eosinophilic Asthma |
| 投稿时间：2022-06-05 修订日期：2022-06-30 |
| DOI：10.13241/j.cnki.pmb.2022.21.021 |
| 中文关键词: 嗜酸粒细胞哮喘 2 型固有免疫细胞 糖皮质激素 |
| 英文关键词: Eosinophilic asthma ILC2 Glucocorticoids |
| 基金项目:广东省基础和应用研究基金项目（2020A1515011147） |
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| 中文摘要: |
| 摘要 目的：探究糖皮质激素对嗜酸粒细胞哮喘(Eosinophilic asthma, EA) 2 型固有免疫细胞(Type 2 innate lymphoid cells, ILC2s)的影响及相关机制。方法：研究对象来自我院 2021年6月至 2022年6月的EA患者和健康对照（Healthy control, HC），收集相应临床基线资料并评估病情、进行血常规、肺功能等检查；应用流式细胞术检测外周血单个核细胞（Peripheral blood mononuclear cell, PBMC） ILC2s(CD45+Lin-CD127+CD294+)；ELISA检测外周血IL-5、IL-13浓度。糖皮质激素治疗EA 患者3月后，观察PBMC中ILC2s及IL-5、IL-13浓度。C57BL/6J小鼠给予鸡卵清蛋白(Ovalbumin，OVA) 20 μg 腹腔注射致敏后用1%OVA雾化吸入激发哮喘EA模型，阴性对照（Negative control, NC）组小鼠用同等体积PBS作为对照。EA造模成功的小鼠通过流式细胞术检测血液及肺泡灌洗液中ILC2s，HE染色检测小鼠肺泡灌洗液中嗜酸性粒细胞(Eosinophil, EOS)及肺部炎症。EA小鼠经糖皮质激素处理后，检测肺部炎症情况；流式细胞术检测PBMC、肺泡灌洗液（Bronchoalveolar lavage fluid, BALF）中 ILC2s；分离肺组织ILC2s，western blot检测相关蛋白表达情况。结果：EA组的ILC2s比例升高， EOS升高，2型细胞因子IL-5、IL-13增加，糖皮质激素治疗1月及3月后ILC2s比例下降，2型细胞因子IL-5、IL-13下降。与NC组小鼠比较，EA组小鼠PBMC及BALF中ILC2s升高，BALF中EOS升高，血清中2型细胞因子IL-5、IL-13升高，肺部炎症加重。糖皮质激素治疗后，肺部炎症减轻，EOS下降，ILC2s减少，2型细胞因子IL-5、IL-13下降，下调JAK/STAT蛋白。结论：在EA中，糖皮质激素通过下调JAK/STAT蛋白抑制ILC2s的功能减轻肺部炎症，为激素治疗嗜酸性粒细胞哮喘的机制提供了新方向。 |
| 英文摘要: |
| ABSTRACT Objective: To observe the effect of glucocorticoids on type 2 innate lymphoid cells (ILC2s) in eosinophilic asthma (EA), and to explore the effect of glucocorticoids on ILC2s. Methods: From June 2021 to June 2022, the research subjects were recruited in the Fifth Affiliated Hospital of Sun Yat-sen University. The general data, induced sputum, blood indexes and pulmonary function of the research subjects were collected. The ratio of ILC2s (CD45+Lin-CD127+CD294+) in peripheral blood PBMC were detected by flow cytometry. Cytokines IL-5 and IL-13 in serum were tested by ELISA. The EA patients were treated with glucocorticoid for 3 months. C57BL/6J mice were sensitized by intraperitoneal injection of chicken ovalbumin (Ovalbumin, OVA) with 20 μg, and then was stimulated by inhalation of 1% OVA, which was the EA asthma model. The negative control (NC) group mice were treated with the same volume of PBS. The number of eosinophils was counted; The lung tissue of the mice in each group was stained with HE to observe the inflammation. Flow cytometry was used to detect the changes in the proportion of ILC2s in peripheral blood PBMC and bronchoalveolar lavage in each group. After glucocorticoid treatment, in the EA mouse model, the inflammation of lung and ILC2s in peripheral blood and bronchoalveolar lavage fluid were observed; ILC2s were isolated from lung tissue, and the expression of related proteins was evaluated by western blot. Results: The proportion of ILC2s, EOS, IL-5 and IL-13 were increased in the EA group. After glucocorticoids therapy for 3 months, the proportion of ILC2s, IL-5 and IL-13 were significantly decreased. In addition, in EA mouse model, ILC2s in PBMC and BALF, EOS in BALF and type 2 cytokines IL-5 and IL-13 in serum were increased, but the lung Inflammation was worsened compared with NC. After glucocorticoid treatment, inflammation of lung was alleviated and EOS, ILC2s, IL-5 and IL-13 were decreased. Furtherly, in vitro stimulation of isolated ILC2s found that JAK/STAT protein were proved to be involved in regulating ILC2s activity under the glucocorticoid treatment. Conclusion: Glucocorticoid administration could be effective in treating EA by regulating ILC2s via JAK-STAT signaling pathways, which provides a new direction for the mechanism of hormone therapy for eosinophilic asthma. |
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