哮喘脱离过敏原之后的持续性与促Th2（细胞反应）髓源性树突状细胞的活化相关
2016/01/29
摘要
背景：支气管哮喘的自然病程在一些病人身上包括疾病的缓解期，但是其内在机制尚不清楚。
目的：该研究旨在探索脱离过敏原后控制良好的职业性哮喘患者，其1型髓源性树突状细胞（myeloid dendritic cell，mDCs）功能异常是否会导致哮喘的持续性。
方法：我们招募了32例职业性哮喘患者，他们通过特异性吸入激发试验来确认对面粉或橡胶过敏，并且他们随后不再暴露于这些过敏原。每例受试者通过白细胞分离法分离并标记1型mDCs，并通过与来自对照组的同型异体CD4+ T细胞进行共培养来研究他们的功能。
结果：在随访中，32例受试者中有11例受试者（34%）由于缺乏症状及对组胺非特异性气道高反应性，而被认为处于缓解期。与缓解期哮喘患者比较，持续期哮喘患者的mDCs通过CD4+ T细胞使IL-5、IL-13产量增加，并通过过敏原刺激上调程序性凋亡配体-2（PD-L2）水平。此外，IL-5、IL-13应答可被外源性IL-12及PD-L2阻滞剂所逆转。
讨论：这个研究表明，在哮喘受试者脱离相关过敏原暴露后，mDCs促Th2（细胞反应）特征与哮喘的活动性相关。这些发现同时也强调树突状细胞可以灵活介导Th2编程，并且可以由PD-L2部分介导。
Persistence of asthma following allergen avoidance is associated with proTh2 myeloid dendritic cell activation
Froidure A, Vandenplas O, D’Alpaos V, Evrard G, Pilette C.
Thorax 2015; 0: 1–7. doi:10.1136/ thoraxjnl-2014-206364
ABSTRACT
Background: The natural history of asthma includes in some patients periods of disease remission, but the underlying mechanisms are unknown.
Objectives: We explored whether type 1 myeloid dendritic cell (mDC) dysfunction could be involved in the persistence of asthma, studying the controlled setting of occupational asthma after allergen avoidance.
Methods: We recruited 32 patients with occupational asthma to flour or latex ascertained by specific inhalation challenge and who were no longer exposed to the causal allergen. Leukapheresis was performed in each patient to isolate and characterise blood type 1 mDCs, and their functionality was studied in coculture with allogeneic CD4+ T cells from controls.
Results: At follow-up, 11/32 patients (34%) were characterised by the absence of symptoms and nonspecific bronchial hyper-responsiveness to histamine and were considered to be cured. When compared with cured patients, mDCs from patients with persistent disease increased the production of interleukin (IL) 5 and IL-13 by CD4+ T cells, and upregulated programmed death ligand 2 (PD-L2) upon allergen pulsing. In addition, IL-5 and IL-13 responses could be reversed by exogenous IL-12, as well as by PD-L2 blockade.
Conclusions: This study indicates that pro-Th2 features of mDCs correlate with disease activity in asthma after cessation of exposure to the causal allergen. The findings also highlight that the Th2 programming by dendritic cells is flexible and partly mediated by PD-L2.
背景：支气管哮喘的自然病程在一些病人身上包括疾病的缓解期，但是其内在机制尚不清楚。
目的：该研究旨在探索脱离过敏原后控制良好的职业性哮喘患者，其1型髓源性树突状细胞（myeloid dendritic cell，mDCs）功能异常是否会导致哮喘的持续性。
方法：我们招募了32例职业性哮喘患者，他们通过特异性吸入激发试验来确认对面粉或橡胶过敏，并且他们随后不再暴露于这些过敏原。每例受试者通过白细胞分离法分离并标记1型mDCs，并通过与来自对照组的同型异体CD4+ T细胞进行共培养来研究他们的功能。
结果：在随访中，32例受试者中有11例受试者（34%）由于缺乏症状及对组胺非特异性气道高反应性，而被认为处于缓解期。与缓解期哮喘患者比较，持续期哮喘患者的mDCs通过CD4+ T细胞使IL-5、IL-13产量增加，并通过过敏原刺激上调程序性凋亡配体-2（PD-L2）水平。此外，IL-5、IL-13应答可被外源性IL-12及PD-L2阻滞剂所逆转。
讨论：这个研究表明，在哮喘受试者脱离相关过敏原暴露后，mDCs促Th2（细胞反应）特征与哮喘的活动性相关。这些发现同时也强调树突状细胞可以灵活介导Th2编程，并且可以由PD-L2部分介导。
(马利 张红萍 王刚 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Thorax 2015; 0: 1–7. doi:10.1136/ thoraxjnl-2014-206364）
（Thorax 2015; 0: 1–7. doi:10.1136/ thoraxjnl-2014-206364）
Persistence of asthma following allergen avoidance is associated with proTh2 myeloid dendritic cell activation
Froidure A, Vandenplas O, D’Alpaos V, Evrard G, Pilette C.
Thorax 2015; 0: 1–7. doi:10.1136/ thoraxjnl-2014-206364
ABSTRACT
Background: The natural history of asthma includes in some patients periods of disease remission, but the underlying mechanisms are unknown.
Objectives: We explored whether type 1 myeloid dendritic cell (mDC) dysfunction could be involved in the persistence of asthma, studying the controlled setting of occupational asthma after allergen avoidance.
Methods: We recruited 32 patients with occupational asthma to flour or latex ascertained by specific inhalation challenge and who were no longer exposed to the causal allergen. Leukapheresis was performed in each patient to isolate and characterise blood type 1 mDCs, and their functionality was studied in coculture with allogeneic CD4+ T cells from controls.
Results: At follow-up, 11/32 patients (34%) were characterised by the absence of symptoms and nonspecific bronchial hyper-responsiveness to histamine and were considered to be cured. When compared with cured patients, mDCs from patients with persistent disease increased the production of interleukin (IL) 5 and IL-13 by CD4+ T cells, and upregulated programmed death ligand 2 (PD-L2) upon allergen pulsing. In addition, IL-5 and IL-13 responses could be reversed by exogenous IL-12, as well as by PD-L2 blockade.
Conclusions: This study indicates that pro-Th2 features of mDCs correlate with disease activity in asthma after cessation of exposure to the causal allergen. The findings also highlight that the Th2 programming by dendritic cells is flexible and partly mediated by PD-L2.
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肺活量校正的呼出气一氧化碳(FeNO)水平有利于儿童、青少年及青壮年哮喘的诊断
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哮喘儿童及青少年的体质指数，脂肪因子和胰岛素抵抗情况
