糖皮质激素治疗通过STAT通路抑制哮喘患者的ILC2的活性及活动频率
2018/06/04
摘要
背景：2型先天性淋巴细胞（ILC2）与哮喘密切相关。然而，目前暂无关于糖皮质激素对哮喘患者ILC2s影响的前瞻性研究。本研究的目的是开展关于评估哮喘患者接受糖皮质激素治疗后的ILC2活性的前瞻性研究。
方法：给予哮喘或哮喘伴过敏性鼻炎的患者为期3个月的糖皮质激素治疗，评估其循环ILC2水平，并进行体外研究探讨糖皮质激素影响ILC2s可能的信号传导途径。
结果：治疗后第1个月和第3个月患者症状控制良好，循环ILC2水平显著降低。糖皮质激素显著降低过敏患者外周血中为应对IL-25，IL-33和IL-2而产生IL-5，IL-13和IL-9的单核细胞数水平。此外，ILC2s是IL-5，IL-13和IL-9的主要来源，糖皮质激素治疗可降低其水平。STAT3，STAT5，STAT6，JAK3和MEK信号通路被证明参与糖皮质激素治疗对ILC2活性的调节。
结论：数据表明，糖皮质激素可通过MEK / JAK-STAT信号通路调节ILC2s治疗哮喘。这为糖皮质激素治疗过敏性疾病提供了新理解。
ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma.
Yu QN, et al. Allergy;2018,Mar 15. Abstract
Abstract
BACKGROUND:Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients.
METHODS:The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signaling pathways were investigated in vitro.
RESULTS:The patients were well-controlled and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL-5, IL-13 and IL-9 in response to IL-25, IL-33 plus IL-2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL-5, IL-13 and IL-9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signaling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment.
CONCLUSIONS:The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK-STAT signaling pathways. This provides a new understanding of glucocorticoid application in regards to allergic diseases.
背景：2型先天性淋巴细胞（ILC2）与哮喘密切相关。然而，目前暂无关于糖皮质激素对哮喘患者ILC2s影响的前瞻性研究。本研究的目的是开展关于评估哮喘患者接受糖皮质激素治疗后的ILC2活性的前瞻性研究。
方法：给予哮喘或哮喘伴过敏性鼻炎的患者为期3个月的糖皮质激素治疗，评估其循环ILC2水平，并进行体外研究探讨糖皮质激素影响ILC2s可能的信号传导途径。
结果：治疗后第1个月和第3个月患者症状控制良好，循环ILC2水平显著降低。糖皮质激素显著降低过敏患者外周血中为应对IL-25，IL-33和IL-2而产生IL-5，IL-13和IL-9的单核细胞数水平。此外，ILC2s是IL-5，IL-13和IL-9的主要来源，糖皮质激素治疗可降低其水平。STAT3，STAT5，STAT6，JAK3和MEK信号通路被证明参与糖皮质激素治疗对ILC2活性的调节。
结论：数据表明，糖皮质激素可通过MEK / JAK-STAT信号通路调节ILC2s治疗哮喘。这为糖皮质激素治疗过敏性疾病提供了新理解。
(中国医科大学附属第一医院呼吸与危重症医学科 李文扬 摘译 杨冬 审校)
(Yu QN, et al. Allergy;2018,Mar 15. Abstract)
(Yu QN, et al. Allergy;2018,Mar 15. Abstract)
ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma.
Yu QN, et al. Allergy;2018,Mar 15. Abstract
Abstract
BACKGROUND:Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients.
METHODS:The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signaling pathways were investigated in vitro.
RESULTS:The patients were well-controlled and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL-5, IL-13 and IL-9 in response to IL-25, IL-33 plus IL-2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL-5, IL-13 and IL-9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signaling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment.
CONCLUSIONS:The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK-STAT signaling pathways. This provides a new understanding of glucocorticoid application in regards to allergic diseases.
