浆样树突状细胞可引起急性哮喘急性发作
2018/09/10
摘要
背景：虽然由病毒引发的急性发作占哮喘住院患者的大部分，但急性发作所涉及的病理生理机制仍知之甚少。浆样树突状细胞（pDC），是抗病毒免疫中重要细胞，具有促炎或致耐受功能，但是其在哮喘急性发作中的作用仍未知。
目标：研究浆样树突状细胞在过敏性气道炎症及哮喘急性发作中的作用。
方法：用过敏性气道疾病（AAD）和病毒诱导的过敏性气道疾病恶化的动物模型分析体内浆样树突状细胞的功能及其所参与的潜在机制。进一步研究稳定期或急性发作期哮喘患者的痰以确定pDC是否存在及其与炎症的相关性。
结果：浆样树突状细胞是驱动哮喘急性发作的免疫炎症级联反应的关键介质。在过敏性气道疾病及鼻病毒诱导的过敏性气道疾病恶化的动物模型中，浆样树突状细胞在炎症期间募集到肺并迁移到淋巴结以增强TH2介导的效应反应。因此，过敏原激发后或鼻病毒感染期间的浆样树突状细胞的消耗消除了炎症和疾病的恶化。此过程的核心是IL-25，其由过敏原刺激或感染鼻病毒及条件性浆样树突状细胞的促炎功能诱导。同样地，在哮喘患者中，浆样树突状细胞数量在急性发作期显着增加并且与炎症的严重程度和哮喘发作的风险相关。
结论：我们的研究揭示了浆样树突状细胞在哮喘急性发作中既往未曾预料到的作用，具有潜在诊断和预后意义。同时提议急性哮喘中浆样树突状细胞和IL-25的靶向治疗。
Plasmacytoid dendritic cells drive acute asthma exacerbations
Chairakaki AD, Saridaki MI.
METHODS:Animal models of allergic airway disease (AAD) and virus-induced AAD exacerbations were used to dissect pDC function in vivo and unwind the potential mechanisms involved. Sputum from asthmatic patients with stable disease or acute exacerbations was further studied to determine the presence of pDCs and correlation with inflammation.
RESULTS:pDCs were key mediators of the immunoinflammatory cascade that drives asthma exacerbations. In animal models of AAD and rhinovirus-induced AAD exacerbations, pDCs were recruited to the lung during inflammation and migrated to the draining lymph nodes to boost TH2-mediated effector responses. Accordingly, pDC depletion after allergen challenge or during rhinovirus infection abrogated exacerbation of inflammation and disease. Central to this process was IL-25, which was induced by allergen challenge or rhinovirus infection and conditioned pDCs for proinflammatory function. Consistently, in asthmatic patients pDC numbers were markedly increased during exacerbations and correlated with the severity of inflammation and the risk for asthma attacks.
CONCLUSIONS:Our studies uncover a previously unsuspected role of pDCs in asthma exacerbations with potential diagnostic and prognostic implications. They also propose the therapeutic targeting of pDCs and IL-25 for the treatment of acute asthma.
背景：虽然由病毒引发的急性发作占哮喘住院患者的大部分，但急性发作所涉及的病理生理机制仍知之甚少。浆样树突状细胞（pDC），是抗病毒免疫中重要细胞，具有促炎或致耐受功能，但是其在哮喘急性发作中的作用仍未知。
目标：研究浆样树突状细胞在过敏性气道炎症及哮喘急性发作中的作用。
方法：用过敏性气道疾病（AAD）和病毒诱导的过敏性气道疾病恶化的动物模型分析体内浆样树突状细胞的功能及其所参与的潜在机制。进一步研究稳定期或急性发作期哮喘患者的痰以确定pDC是否存在及其与炎症的相关性。
结果：浆样树突状细胞是驱动哮喘急性发作的免疫炎症级联反应的关键介质。在过敏性气道疾病及鼻病毒诱导的过敏性气道疾病恶化的动物模型中，浆样树突状细胞在炎症期间募集到肺并迁移到淋巴结以增强TH2介导的效应反应。因此，过敏原激发后或鼻病毒感染期间的浆样树突状细胞的消耗消除了炎症和疾病的恶化。此过程的核心是IL-25，其由过敏原刺激或感染鼻病毒及条件性浆样树突状细胞的促炎功能诱导。同样地，在哮喘患者中，浆样树突状细胞数量在急性发作期显着增加并且与炎症的严重程度和哮喘发作的风险相关。
结论：我们的研究揭示了浆样树突状细胞在哮喘急性发作中既往未曾预料到的作用，具有潜在诊断和预后意义。同时提议急性哮喘中浆样树突状细胞和IL-25的靶向治疗。
（中日友好医院呼吸与危重症医学科 张鑫 摘译 林江涛 审校）
（J Allergy Clin Immunol. 2018 Aug;142(2):542-556.）
（J Allergy Clin Immunol. 2018 Aug;142(2):542-556.）
Plasmacytoid dendritic cells drive acute asthma exacerbations
Chairakaki AD, Saridaki MI.
Abstract
BACKGROUND:Although acute exacerbations, mostly triggered by viruses, account for the majority of hospitalizations in asthmatic patients, there is still very little known about the pathophysiologic mechanisms involved. Plasmacytoid dendritic cells (pDCs), prominent cells of antiviral immunity, exhibit proinflammatory or tolerogenic functions depending on the context, yet their involvement in asthma exacerbations remains unexplored.
OBJECTIVES:We sought to investigate the role of pDCs in allergic airway inflammation and acute asthma exacerbations.METHODS:Animal models of allergic airway disease (AAD) and virus-induced AAD exacerbations were used to dissect pDC function in vivo and unwind the potential mechanisms involved. Sputum from asthmatic patients with stable disease or acute exacerbations was further studied to determine the presence of pDCs and correlation with inflammation.
RESULTS:pDCs were key mediators of the immunoinflammatory cascade that drives asthma exacerbations. In animal models of AAD and rhinovirus-induced AAD exacerbations, pDCs were recruited to the lung during inflammation and migrated to the draining lymph nodes to boost TH2-mediated effector responses. Accordingly, pDC depletion after allergen challenge or during rhinovirus infection abrogated exacerbation of inflammation and disease. Central to this process was IL-25, which was induced by allergen challenge or rhinovirus infection and conditioned pDCs for proinflammatory function. Consistently, in asthmatic patients pDC numbers were markedly increased during exacerbations and correlated with the severity of inflammation and the risk for asthma attacks.
CONCLUSIONS:Our studies uncover a previously unsuspected role of pDCs in asthma exacerbations with potential diagnostic and prognostic implications. They also propose the therapeutic targeting of pDCs and IL-25 for the treatment of acute asthma.
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年轻人与老年人不同上呼吸道微生物菌群及其哮喘相关功能基因
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过敏性气道致敏作用会损害细菌性呼吸道感染期间的抗菌IgG抗体反应
