Zytoskelettdynamik und Kraftgenerierung wandernder Leukozyten

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Dendritic cells are potent primers of naïve T cells. Their function in vivo is highly dependent on their directed migration from the periphery where they take up antigens, towards the draining lymph node where they present the processed antigen to T cells. The main determinants that define the positioning and trafficking of leukocytes are chemokines that dictate the direction of migration and integrins that mediate the physical interaction with the cellular and extracellular environment. On leukocytes the functional state of integrins is controlled via chemokines. Using a genetic approach it will first be investigated in vivo which integrin families are responsible for which step during the migration of DC from the skin into the draining lymph node. Migratory or positioning defects will be studied in detail using video microscopy based in vitro assays. It will be defined at which level the chemotactic response is disturbed in the absence of integrins. Therefore, gradient sensing, cell polarization, adhesiveness, migration speed and directionality will be analyzed separately.