Rho-Family GTPase Cdc42 Controls Migration of Langerhans Cells In Vivo
Rho-Family GTPase Cdc42 Controls Migration of Langerhans Cells In Vivo
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DOI：
10.4049/jimmunol.1201082
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发表时间：
2013-01-01
影响因子：
4.4
通讯作者：
Brocker, Thomas
中科院分区：
文献类型：
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作者：
Luckashenak, Nancy;Waehe, Anna;Brocker, Thomas
皮肤的表皮朗格汉斯细胞（LC）代表原型迁移树突状细胞（DC）亚型。在皮肤中，它们吸收Ag，迁移到引流淋巴结，并有助于Ag运输和免疫。LC的不同消耗模型揭示了这种细胞类型的对比作用和贡献。为了靶向DCs的迁移特性，我们产生了在DCs中特异性缺乏Rho家族GTdcdc 42的小鼠。在这些动物中，表皮与LC的初始接种是功能性的，导致朗格汉斯细胞数量略有减少。然而，Cdc 42缺陷型LC不能在稳态以及刺激后离开皮肤，因为它们不进入皮肤引流传入淋巴管。类似地，其他Cdc 42缺陷的迁移性DC亚群也不能正确地归巢到相应的引流淋巴结。我们使用这种新的小鼠模型，其中LC被锁定，以证明这些细胞大大有助于引发Ag特异性的CD 4和CD 8 T细胞反应后，表皮免疫，但不能检测到的作用，在诱导接触超敏反应的各种剂量的半抗原。免疫学杂志，2013，190：27-35。
Epidermal Langerhans cells (LCs) of the skin represent the prototype migratory dendritic cell (DC) subtype. In the skin, they take up Ag, migrate to the draining lymph nodes, and contribute to Ag transport and immunity. Different depletion models for LCs have revealed contrasting roles and contributions of this cell type. To target the migratory properties of DCs, we generated mice lacking the Rho-family GTPase Cdc42 specifically in DCs. In these animals, the initial seeding of the epidermis with LCs is functional, resulting in slightly reduced Langerhans cell numbers. However, Cdc42-deficient LCs fail to leave the skin in steady state as well as upon stimulation, as they do not enter the skin-draining afferent lymph vessels. Similarly, also other Cdc42-deficient migratory DC subsets fail to home properly to the corresponding draining lymph nodes. We used this novel mouse model, in which LCs are locked out, to demonstrate that these cells contribute substantially to priming of Ag-specific CD4 and CD8 T cell responses upon epicutaneous immunization, but could not detect a role in the induction of contact hypersensitivity to various doses of hapten. The Journal of Immunology, 2013, 190: 27-35.