对哮喘患者使用糖皮质激素治疗能通过STAT通路抑制哮喘患者ILC2频率和活性
2018/04/04
摘要
背景及目的：2组固有淋巴细胞（ILC2）与哮喘密切相关。然而，没有关于糖皮质激素对哮喘患者ILC2s影响的前瞻性研究。我们的目的是对哮喘患者进行糖皮质激素治疗后ILC2的活性进行评估及前瞻性研究。
方法：对合并过敏性鼻炎的哮喘患者和不合并过敏性鼻炎的哮喘患者用糖皮质激素治疗3个月。评估循环ILC2水平。体外评估糖皮质激素对ILC2s活性及其可能相关的信号传导通路的影响。
结果：治疗后第1个月和第3个月患者病情控制良好，ILC2水平显著降低。合并过敏性鼻炎的哮喘患者的外周血单核细胞在IL-25，IL-33及IL-2的刺激下产生大量IL-5，IL-13和IL-9，糖皮质激素能显著降低它们的水平。此外，ILC2s被确定为IL-5，IL-13和IL-9的主要来源，且糖皮质激素治疗能够逆转它们的高水平。在糖皮质激素治疗下，STAT3，STAT5，STAT6，JAK3和MEK信号通路被证明参与调节ILC2活性。
结论：以上数据表明，糖皮质激素的应用能通过MEK / JAK-STAT信号通路调节ILC2s从而有效治疗哮喘，同时提供了对于过敏性疾病使用糖皮质激素的新理念。
ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma
Yu QN, Guo YB, Li X.
Abstract
BACKGROUND AND OBJECTIVES: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.
背景及目的：2组固有淋巴细胞（ILC2）与哮喘密切相关。然而，没有关于糖皮质激素对哮喘患者ILC2s影响的前瞻性研究。我们的目的是对哮喘患者进行糖皮质激素治疗后ILC2的活性进行评估及前瞻性研究。
方法：对合并过敏性鼻炎的哮喘患者和不合并过敏性鼻炎的哮喘患者用糖皮质激素治疗3个月。评估循环ILC2水平。体外评估糖皮质激素对ILC2s活性及其可能相关的信号传导通路的影响。
结果：治疗后第1个月和第3个月患者病情控制良好，ILC2水平显著降低。合并过敏性鼻炎的哮喘患者的外周血单核细胞在IL-25，IL-33及IL-2的刺激下产生大量IL-5，IL-13和IL-9，糖皮质激素能显著降低它们的水平。此外，ILC2s被确定为IL-5，IL-13和IL-9的主要来源，且糖皮质激素治疗能够逆转它们的高水平。在糖皮质激素治疗下，STAT3，STAT5，STAT6，JAK3和MEK信号通路被证明参与调节ILC2活性。
结论：以上数据表明，糖皮质激素的应用能通过MEK / JAK-STAT信号通路调节ILC2s从而有效治疗哮喘，同时提供了对于过敏性疾病使用糖皮质激素的新理念。
(中日友好医院呼吸与危重症医学科 张科文 摘译 林江涛 审校)
(Allergy.2018 Mar 15. doi: 10.1111/all.13438 )
(Allergy.2018 Mar 15. doi: 10.1111/all.13438 )
ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma
Yu QN, Guo YB, Li X.
Abstract
BACKGROUND AND OBJECTIVES: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.
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比较老年哮喘或老年非哮喘与年轻哮喘患者之间临床、生理和炎症特征
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哮喘中气道病理异质性：使用拓扑数据分析可视化疾病微团簇
