Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment
Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment
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DOI：
10.1016/j.jaci.2004.11.043
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发表时间：
2005-04-01
影响因子：
14.2
通讯作者：
Gosset, P
中科院分区：
文献类型：
--
作者：
Pichavant, M;Charbonnier, AS;Gosset, P
背景：气道树突状细胞（DCs）在过敏性哮喘的致敏和炎症反应中起重要作用。目的：由于屋尘螨半胱氨酸蛋白酶变应原Der p 1可诱导支气管上皮细胞（BEC）产生趋化因子，本研究旨在探讨Der p 1对支气管上皮细胞（BEC）募集DC的能力。通过前体、未成熟和成熟单核细胞衍生的DC（MDDC）和CD 34（+）衍生的朗格汉斯细胞（LC）的迁移，评估支气管上皮细胞系BEAS-2B和来自非特异性对照和过敏性哮喘患者的BEC的趋化活性。暴露于Der p 1后，BEAS-2B和BEC产生的C-C趋化因子配体（CCL）-2，CCL 5和C-X-C趋化因子配体10增加，而缺乏酶活性的酶原proDer p 1没有影响。来自两组的BEAS-2B和BEC的Der p I刺激显著增加MDDC前体的募集，这取决于CCL 2、CCL 5和C-X-C趋化因子配体10的产生。在重建的极化上皮中，Der p I的顶端应用增强了MDDC前体向上皮层的迁移。此外，哮喘患者的BEC的Der p 1刺激增加了LC前体的迁移，这主要取决于CCL 20的分泌，而对照组则没有。未成熟和成熟的DCs没有迁移observed.Conclusion：这些数据证实，BECs通过分泌趋化因子参与支气管上皮内DC网络的稳态。在过敏性哮喘中，CCL 20产生的上调诱导LC募集，其作用仍有待确定。
Background: Airway dendritic cells (DCs) are crucial for allergen-induced sensitization and inflammation in allergic asthma. After allergen challenge, an increased number of DCs is observed in airway epithelium from patients with allergy.Objective: Because Der p 1, a cysteine protease allergen from Dermatophagoides pteronyssinus, induces chemokine production by bronchial epithelial cells (BECs), the purpose of this investigation was to evaluate the capacity of BEC exposed to Der p 1 to recruit DCs.Methods: Chemotactic activity of BEAS-2B, a bronchial epithelial cell line, and BECs from nonatopic controls and patients with allergic asthma was evaluated on the migration of precursors, immature and mature monocyte-derived DCs (MDDCs), and CD34(+)-derived Langerhans cells (LCs).Results: C-C chemokine ligand (CCL)-2, CCL5, and C-X-C chemokine ligand 10 production by BEAS-2B and BEC was increased after Der p 1 exposure, whereas the proenzyme proDer p 1 devoid of enzymatic activity had no effect. Der p I stimulation of BEAS-2B and BEC from both groups increased significantly the recruitment of MDDC precursors, depending on CCL2, CCL5, and C-X-C chemokine ligand 10 production. In a reconstituted polarized epithelium, apical application of Der p I enhanced MDDC precursor migration into the epithelial layer. Moreover, Der p 1 stimulation of BEC from patients with asthma but not from controls increased the migration of LC precursors, mainly dependent on CCL20 secretion. No migration of immature and mature DCs was observed.Conclusion: These data confirmed that BECs participate in the homeostasis of the DC network present within the bronchial epithelium through the secretion of chemokines. In allergic asthma, upregulation of CCL20 production induced LC recruitment, the role of which remains to be determined.