Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation
Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation
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DOI：
10.1172/jci8107
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发表时间：
2000-08-01
影响因子：
15.9
通讯作者：
Pauwels, RA
中科院分区：
文献类型：
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作者：
Lambrecht, BN;De Veerman, M;Pauwels, RA
本研究旨在探讨树突状细胞（DCs）在过敏性哮喘小鼠模型中是否能诱导对气传过敏原的致敏作用。将卵清蛋白致敏（OVA致敏）或未致敏的髓样DCs注入未致敏小鼠的气道后，它们迁移至纵隔淋巴结。2周后用OVA气雾剂激发时，活化的CD4和CD8淋巴细胞、嗜酸性粒细胞和中性粒细胞被募集到主动免疫小鼠的肺部。这些CD4⁺淋巴细胞主要产生白细胞介素 - 4（IL - 4）和白细胞介素 - 5（IL - 5），也产生干扰素 - γ（IFN - γ），而CD8⁺淋巴细胞主要产生干扰素 - γ。组织学分析显示血管周围和支气管周围嗜酸性粒细胞浸润以及杯状细胞增生。对白细胞介素 - 4基因敲除（IL - 4⁻/⁻）和CD28基因敲除（CD28⁻/⁻）小鼠的研究表明，宿主细胞产生白细胞介素 - 4以及DCs为T细胞提供共刺激对于诱导该反应至关重要。肺部CD4⁺T细胞强烈表达Th2标志物T1/ST2，并且通过DCs表达的配体经由该分子进行的信号传导对于气道嗜酸性粒细胞增多症的形成至关重要。这些数据表明，气道中的DCs可诱导对吸入性抗原的致敏作用，并且这些细胞表面表达的分子对于Th2依赖性气道嗜酸性粒细胞增多症的发展至关重要。
The aim of this study was to investigate whether dendritic cells (DCs) can induce sensitization to aeroallergen in a mouse model of allergic asthma. Ovalbumin-pulsed (OVA-pulsed) or unpulsed myeloid DCs that were injected into the airways of naive mice migrated into the mediastinal lymph nodes. When challenged 2 weeks later with an aerosol of OVA, activated CD4 and CD8 lymphocytes, eosinophils, and neutrophils were recruited to the lungs of actively immunized mice. These CD4(+) lymphocytes produced predominantly IL-4 and IL-5 but also IFN-gamma, whereas CD8(+) lymphocytes produced predominantly IFN-gamma. Histological analysis revealed perivascular and peribronchial eosinophilic infiltrates and goblet cell hyperplasia. Studies in IL-4(-/-) and CD28(-/-) mice revealed that production of IL-4 by host cells and provision of costimulation to T cells by DCs were critical for inducing the response. Lung CD4(+) T cells strongly expressed the Th2 marker T1/ST2, and signaling through this molecule via a ligand expressed on DCs was essential for the establishment of airway eosinophilia. These data demonstrate that DCs in the airways induce sensitization to inhaled antigen and that molecules expressed on the surface of these cells are critical for the development of Th2-dependent airway eosinophilia.