过敏原诱导哮喘患者痰2型固有淋巴细胞水平增加
2018/01/15
原理:2型固有淋巴细胞(ILC2)是2型细胞因子的重要来源之一,在小鼠哮喘模型中启动嗜酸粒细胞性炎症反应。
目的:研究ILC2在过敏原诱导过敏哮喘患者气道嗜酸粒细胞性炎症反应中的作用。
方法:采用溶剂对照的过敏原激发交叉试验,在试验过程中所有受试者(n = 10)均表现出过敏原诱导的早期和晚期反应、气道嗜酸粒细胞增多及气道乙酰甲胆碱反应性增加,在吸入激发试验前后采集骨髓、血和痰标本。
测量和主要结果:采用流式细胞术检测ILC2(lin-FcεRI-CD45+CD127+ST2+)、CD4+T淋巴细胞以及IL-5和IL-13的表达。体外试验探索ILC2和CD4+T细胞的激素敏感性。过敏原激发后24小时,痰中总ILC2、IL-5+ ILC2、IL-13+ ILC2和CRTH2+ ILC2均有显著增加,对应血中ILC2显著减少。过敏原激发后24和48小时,痰中总CD4+T细胞、IL-5+ CD4+T细胞和IL-13+ CD4+T细胞显著增加,而CRTH2+ CD4+T细胞无明显变化。在血和骨髓中,仅CD4+T细胞在过敏原激发后显示出活性增强。气道嗜酸粒细胞在所有时间点与IL-5+ ILC2相关,在过敏原激发后48小时与过敏原诱导的IL-5+ CD4+细胞改变相关。在两种细胞类型中,地塞米松均显著抑制了IL-2和IL-33刺激的IL-5和IL-13产生。
结论:过敏性哮喘反应的气道中固有免疫和获得性免疫细胞增加。总ILC2和2型细胞因子阳性ILC2仅在气道内增加,而CD4+ T淋巴细胞呈现出局部和全身性的增加。两类细胞的激素敏感性也许可以解释轻度哮喘患者激素治疗的效果。
关键词:固有淋巴细胞;嗜酸粒细胞性炎症;过敏性哮喘
(Am J Respir Crit Care Med. 2017;196(6):700-712.DIO: 10.1164/rccm.201612-2427OC.)
Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Subjects with Asthma
Chen R, Smith SG, Salter B, El-Gammal A, Oliveria JP, Obminski C, Watson R, O'Byrne PM, Gauvreau GM, Sehmi R
Am J Respir Crit Care Med. 2017;196(6):700-712.DIO: 10.1164/rccm.201612-2427OC.
Abstract
Rationale: Group 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma.
Objectives: To investigate the role of ILC2 in allergen-induced airway eosinophilic responses in subjects with atopy and asthma.
Methods: Using a diluent-controlled allergen challenge crossover study, where all subjects (n = 10) developed allergen-induced early and late responses, airway eosinophilia, and increased methacholine airway responsiveness, bone marrow, blood, and sputum samples were collected before and after inhalation challenge.
Measurements and Main Results: ILC2 (lin-FcεRI-CD45+CD127+ST2+) and CD4+T lymphocytes were enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression. Steroid sensitivity of ILC2 and CD4+ T cells was investigated in vitro. A significant increase in total, IL-5+, IL-13+, and CRTH2+ ILC2 was found in sputum, 24 hours after allergen, coincident with a significant decrease in blood ILC2. Total, IL-5+, and IL-13+, but not CRTH2+, CD4+ T cells significantly increased at 24 and 48 hours after allergen in sputum. In blood and bone marrow, only CD4+ cells demonstrated increased activation after allergen. Airway eosinophilia correlated with IL-5+ ILC2 at all time points and allergen-induced changes in IL-5+ CD4+ cells at 48 hours after allergen. Dexamethasone significantly attenuated IL-2- and IL-33-stimulated IL-5 and IL-13 production by both cell types.
Conclusions: Innate and adaptive immune cells are increased in the airways associated with allergic asthmatic responses. Total and type 2 cytokine-positive ILC2 are increased only within the airways, whereas CD4+ T lymphocytes demonstrated local and systemic increases. Steroid sensitivity of both cells may explain effectiveness of this therapy in those with mild asthma.
Keywords: innate lymphoid cells; eosinophilic inflammation; allergic asthma
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