在重症哮喘中，嗜酸粒细胞胞外诱捕网通过刺激气道上皮激活2型固有淋巴细胞
2019/11/12
摘要
背景：在重症哮喘（SA）中，嗜酸粒细胞活化释放胞外诱捕网（extracellular traps，EETs），从而导致气道炎症。但是，EETs在固有免疫中的作用尚不十分清楚。本研究旨在证明由EETs介导的重症哮喘气道炎症机制。
方法：在重症哮喘（n = 13），非重症哮喘（NSA，n = 17）和健康对照组（HC，n = 8）中评估EET+嗜酸粒细胞与2型固有淋巴细胞（ILC2s）的外周计数。为了证实EETs的作用，在小鼠中评估气道高反应性（AHR）和适应性/固有免疫反应。此外，还检测了抗IL-33 / TSLP抗体的作用。
结果：重症哮喘中EET+嗜酸粒细胞与ILC2的数量显著增加，两种细胞之间呈正相关（r = 0.539，P <0.001）。当给小鼠注射EETs时，我们观察到支气管肺泡灌洗液（BALF）中上皮来源的细胞因子（IL-1α，IL-1β，CXCL-1，CCL24，IL-33和TSLP）与嗜酸/中性粒细胞计数显著增加，同时肺中产生IL-5或IL-13的ILC2比例增加。当用EETs治疗接受ILC2s的Rag1-/-小鼠时，发现其气道高反应性增加，BALF中IL-5/IL-13水平升高，且它们能被抗IL-33或抗TSLP抗体有效抑制。
结论：EETs可以增强重症哮喘中的固有与2型免疫反应，而上皮靶向生物制剂（抗IL-33/TSLP抗体）可能具有潜在的益处。
Eosinophil extracellular traps activate type 2 innate lymphoid cells through stimulating airway epithelium in severe asthma
Choi Y, Kim YM, Lee HR, Mun J, Sim S, Lee DH, Duy PL, Kim SH, Shin YS, Lee SW, Park HS.
Allergy; 2019; Jul 22. doi: 10.1111/all.13997.
Abstract
BACKGROUND: Activated eosinophils release extracellular traps (EETs), which contribute to airway inflammation in severe asthma (SA). However, the role of EETs in innate immunity has not yet been completely determined. The present study aimed to demonstrate the mechanism of airway inflammation in SA mediated by EETs.
METHODS: Peripheral counts of EET+ eosinophils and type 2 innate lymphoid cells (ILC2s) were evaluated in patients with SA (n = 13), nonsevere asthma (NSA, n = 17), and healthy control subjects (HC, n = 8). To confirm the effect of EETs, airway hyperresponsiveness (AHR) and adapted/innate immune responses were assessed in mice. Furthermore, the effects of anti‐IL‐33/TSLP antibody were tested.
RESULTS: The numbers of EET+ eosinophils and ILC2s were significantly elevated in SA, with a positive correlation between these 2 cells (r = .539, P < .001). When mice were injected with EETs, we observed significant increases in epithelium‐derived cytokines (IL‐1α, IL‐1β, CXCL‐1, CCL24, IL‐33, and TSLP) and eosinophil/neutrophil count in bronchoalveolar lavage fluid (BALF) as well as an increased proportion of IL‐5 or IL‐13‐producing ILC2s in the lungs. When Rag1‐/‐ mice receiving ILC2s were treated with EETs, increased AHR and IL‐5/IL‐13 levels in BALF were noted, which were effectively suppressed by anti‐IL‐33 or anti‐TSLP antibody.
CONCLUSION: EETs could enhance innate and type 2 immune responses in SA, in which epithelium‐targeting biologics (anti‐IL‐33/TSLP antibody) may have a potential benefit.
背景：在重症哮喘（SA）中，嗜酸粒细胞活化释放胞外诱捕网（extracellular traps，EETs），从而导致气道炎症。但是，EETs在固有免疫中的作用尚不十分清楚。本研究旨在证明由EETs介导的重症哮喘气道炎症机制。
方法：在重症哮喘（n = 13），非重症哮喘（NSA，n = 17）和健康对照组（HC，n = 8）中评估EET+嗜酸粒细胞与2型固有淋巴细胞（ILC2s）的外周计数。为了证实EETs的作用，在小鼠中评估气道高反应性（AHR）和适应性/固有免疫反应。此外，还检测了抗IL-33 / TSLP抗体的作用。
结果：重症哮喘中EET+嗜酸粒细胞与ILC2的数量显著增加，两种细胞之间呈正相关（r = 0.539，P <0.001）。当给小鼠注射EETs时，我们观察到支气管肺泡灌洗液（BALF）中上皮来源的细胞因子（IL-1α，IL-1β，CXCL-1，CCL24，IL-33和TSLP）与嗜酸/中性粒细胞计数显著增加，同时肺中产生IL-5或IL-13的ILC2比例增加。当用EETs治疗接受ILC2s的Rag1-/-小鼠时，发现其气道高反应性增加，BALF中IL-5/IL-13水平升高，且它们能被抗IL-33或抗TSLP抗体有效抑制。
结论：EETs可以增强重症哮喘中的固有与2型免疫反应，而上皮靶向生物制剂（抗IL-33/TSLP抗体）可能具有潜在的益处。
(邓稞1 张红萍1 王刚2 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Allergy; 2019; Jul 22. doi: 10.1111/all.13997.）
（Allergy; 2019; Jul 22. doi: 10.1111/all.13997.）
Eosinophil extracellular traps activate type 2 innate lymphoid cells through stimulating airway epithelium in severe asthma
Choi Y, Kim YM, Lee HR, Mun J, Sim S, Lee DH, Duy PL, Kim SH, Shin YS, Lee SW, Park HS.
Allergy; 2019; Jul 22. doi: 10.1111/all.13997.
Abstract
BACKGROUND: Activated eosinophils release extracellular traps (EETs), which contribute to airway inflammation in severe asthma (SA). However, the role of EETs in innate immunity has not yet been completely determined. The present study aimed to demonstrate the mechanism of airway inflammation in SA mediated by EETs.
METHODS: Peripheral counts of EET+ eosinophils and type 2 innate lymphoid cells (ILC2s) were evaluated in patients with SA (n = 13), nonsevere asthma (NSA, n = 17), and healthy control subjects (HC, n = 8). To confirm the effect of EETs, airway hyperresponsiveness (AHR) and adapted/innate immune responses were assessed in mice. Furthermore, the effects of anti‐IL‐33/TSLP antibody were tested.
RESULTS: The numbers of EET+ eosinophils and ILC2s were significantly elevated in SA, with a positive correlation between these 2 cells (r = .539, P < .001). When mice were injected with EETs, we observed significant increases in epithelium‐derived cytokines (IL‐1α, IL‐1β, CXCL‐1, CCL24, IL‐33, and TSLP) and eosinophil/neutrophil count in bronchoalveolar lavage fluid (BALF) as well as an increased proportion of IL‐5 or IL‐13‐producing ILC2s in the lungs. When Rag1‐/‐ mice receiving ILC2s were treated with EETs, increased AHR and IL‐5/IL‐13 levels in BALF were noted, which were effectively suppressed by anti‐IL‐33 or anti‐TSLP antibody.
CONCLUSION: EETs could enhance innate and type 2 immune responses in SA, in which epithelium‐targeting biologics (anti‐IL‐33/TSLP antibody) may have a potential benefit.
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