Molecular mechanisms controlling DC migration in CNS autoimmunity
The trafficking of myeloid cells into and within the central nervous system (CNS) as well as their localized functions are critical in the development of neuroinflammation. These processes are tightly regulated by chemokines and their corresponding receptors. However, the functional implication of dendritic cells (DC), a highly specialized subgroup of myeloid cells, their migration pattern within the CNS and the role of chemokines therein are still ill-defined. Our earlier studies demonstrated that DC expressing the chemokine receptor 4 (CCR4) are cellular mediators of experimental autoimmune encephalomyelitis. This project aims at deciphering the cellular and molecular mechanisms of chemokine-dependent DC migration and the in vivo visualization of DC trafficking and cellular interaction in the CNS under pathophysiological conditions. We will study chemokine-induced intracellular signaling pathways, DC-T cell contact formation and dynamics by live cell imaging. These studies will lead to a better understanding of the fundamental mechanisms of DC migration in neuroinflammation for future therapeutic approaches targeting DC in CNS disorders.