Control of Dendritic Cell Maturation and Migration by the RhoGTPase Regulators SWAP-70 and DEF6.

树突状细胞（DC）的成熟及其随后向淋巴组织的迁移是启动适应性免疫反应和诱导免疫耐受的关键机制。我们最近发表了蛋白质SWAP-70控制DC功能的新机制，例如MHCII分子的上调，s1p介导的迁移和内吞作用，以及自发成熟。SWAP-70通过RhoGTPases的相互作用和调控来调节这些DC功能，特别是RhoA的激活。初步数据显示，除了SWAP-70外，唯一与之密切相关的蛋白DEF6也控制着DCs的自发成熟和迁移。以拮抗的方式，这两种蛋白也控制粘附分子连接素-3的表面表达，这在dc中尚未被描述。本建议旨在了解SWAP-70和DEF6在dc中的综合作用，以开发更连贯的控制机制模型。发现调节这些功能的新元素及其作用机制对了解DC生物学至关重要。

Dendritic cell (DC) maturation and their subsequent migration to lymphoid tissues are key mechanisms to initiate adaptive immune responses and to induce immune tolerance. We have recently published new mechanisms of control of DC function by the protein SWAP-70, e.g. up-regulation of MHCII molecules, S1P-mediated migration and endocytosis, and spontaneous maturation. SWAP-70 regulates these DC functions through interaction and regulation of RhoGTPases, particularly RhoA activation. Preliminary data show that besides SWAP-70, the only closely related protein DEF6 also controls spontaneous maturation and migration of DCs. In an antangonistic manner, both proteins also control surface expression of the adhesion molecule nectin-3, which has not yet been described for DCs. This proposal aims at understanding the combined role of SWAP-70 and DEF6 in DCs to develop a more coherent model of control mechanisms. Discovering new elements regulating these functions and their mechanisms of action is of vital importance to understand DC biology.