Steuerung der Lymphozyten-Migration und des funktionellen Aufbaus lymphatischer Organe durch das Chemokinsystem

适应性免疫反应的发展需要良好的协调机制，以引导循环免疫细胞通过外周组织进入次级淋巴器官。有强有力的实验证据表明，趋化因子及其G蛋白偶联受体负责募集参与炎症过程的细胞，以及白细胞运输的稳态控制和淋巴器官的功能区室化。通过分析趋化因子受体CXCR5或CCR7缺失的小鼠，我们可以确定这两种受体是B淋巴细胞、T淋巴细胞和树突状细胞淋巴组织特异性迁移的主要调节因子。该研究项目旨在进一步阐明体内稳态趋化因子系统的功能，并探索由趋化因子介导的淋巴细胞运输的下游信号决定。基于已建立的趋化因子受体缺失小鼠品系，动物模型和重构实验将进一步有助于我们理解在正常和病理生理免疫反应的某些微环境下决定淋巴细胞亚群选择性迁移和归巢的分子密码。

The development of an adaptive immune response requires wellcoordinated mechanisms in order to navigate circulating immune cells through peripheral tissues and into secondary lymphoid organs. There is strong experimental evidence that chemokines and their G protein-coupled receptors are responsible for recruiting cells involved in inflammatory processes as well as for homeostatic control of leukocyte traffic and functional compartmentalization of lymphoid organs. By analyzing mice deficient for chemokine receptors CXCR5 or CCR7, we could identify both receptors as the principal regulators of lymphoid tissue-specific migration of B and T lymphocytes and dendritic cells. The proposed research project is aimed to elucidate further the function of the homeostatic chemokine systems in vivo and to explore downstream signaling decisions of lymphocyte traffic mediated by chemokines. Based on established mouse strains deficient for chemokine receptors, animal models and reconstitution experiments will further contribute to our understanding of the molecular codes determining the selective migration and homing of lymphocyte subsets in certain microenvironmental settings of normal and pathophysiological immune responses.