Peroxisome proliferator-activated receptor γ inhibits the migration of dendritic cells:: Consequences for the immune response
Peroxisome proliferator-activated receptor γ inhibits the migration of dendritic cells:: Consequences for the immune response
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DOI：
10.4049/jimmunol.170.10.5295
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发表时间：
2003-05-15
影响因子：
4.4
通讯作者：
Trottein, F
中科院分区：
文献类型：
--
作者：
Angeli, W;Hammad, H;Trottein, F
树突状细胞（DC）从上皮细胞向淋巴器官的迁移是一个受严格调控的多步骤事件，参与诱导免疫应答。在这个过程中，脂肪酸衍生物积极和消极调节DC的迁移。在本研究中，我们调查是否激活过氧化物酶体增殖物激活受体（PPARs），一个家庭的核受体激活的天然衍生物的花生四烯酸，可以控制DC迁移从外围网站的Ag捕获引流淋巴结（DLNs）。首先，我们表明，小鼠表皮朗格汉斯细胞（LC）表达PPARgamma，但不表达PPARalpha，mRNA和蛋白质。使用TNF-α诱导的LC迁移的实验小鼠模型，我们表明，高效PPARgamma激动剂罗格列酮特异性地损害LC从表皮的离开。在接触性过敏原诱导的LC迁移模型中，PPARgamma激活不仅阻碍LC迁移及其随后在DLN中作为DC的积累，而且还显著防止了攻击后的接触性超敏反应。最后，在用FITC缀合的Ag进行气管内致敏后，PPARgamma激活抑制了DC从气道粘膜向胸部淋巴结的迁移，并且还显著减少了DLN中Ag特异性T淋巴细胞的引发。我们的研究结果表明，一种新的调节途径，通过PPARgamma的DC迁移从上皮细胞，可能有助于启动免疫反应。
The migration of dendritic cells (DCs) from the epithelia to the lymphoid organs represents a tightly regulated multistep event involved in the induction of the immune response. In this process fatty acid derivatives positively and negatively regulate DC emigration. In the present study we investigated whether activation of peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptors activated by naturally occurring derivatives of arachidonic acid, could control DC migration from the peripheral sites of Ag capture to the draining lymph nodes (DLNs). First, we show that murine epidermal Langerhans cells (LCs) express PPARgamma, but not PPARalpha, mRNA, and protein. Using an experimental murine model of LC migration induced by TNF-alpha, we show that the highly potent PPARgamma agonist rosiglitazone specifically impairs the departure of LCs from the epidermis. In a model of contact allergen-induced LC migration, PPARgamma activation not only impedes LC emigration, and their subsequent accumulation as DCs in the DLNs, but also dramatically prevents the contact hypersensitivity responses after challenge. Finally, after intratracheal sensitization with an FITC-conjugated Ag, PPARgamma activation inhibits the migration of DCs from the airway mucosa to the thoracic LNs and also profoundly reduces the priming of Ag-specific T lymphocytes in the DLNs. Our results suggest a novel regulatory pathway via PPARgamma for DC migration from epithelia that could contribute to the initiation of immune responses.