Induction of plasma membrane ceramides in T cells and their role in functional paralysis

• Antragstellerin: Professorin Dr. Sibylle Schneider-Schaulies
• Fachliche Zuordnung: Anatomie und Physiologie
• Förderung: Förderung von 2010 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 172454098

T cell paralysis is central to the generalised immunosuppression caused by measles virus (MV). At a cellular level, this is reflected by preferential formation of unstable immune synapses (IS) with MV-infected dendritic cells (DCs), which do not support sustained Ca-mobilisation and thereby, activation of scanning T cells. T cell silencing is exerted by the viral glycoprotein complex which, provided on DCs or viral particles, activates sphingomyelinases (SMases) in and membrane ceramides on T cells in a contact dependent manner. This accounts for MV-mediated physical T cell paralysis as reflected by collapse of microvillar extensions, and the inability to T cells to spread and polarise or directionally migrate on substrates. Thus, ceramides might generally modulate T cell signaling-dependent cytoskeletal dynamics which controls essential steps in their activation. We therefore aim to determine the relevance of receptorinduced ceramide membrane platforms in T cells for 1) lateral and vertical recruitment of surface receptors and signaling components, and 2) their role in T cell actin cytoskeletal remodeling in general with 3) emphasis on IS stability and efficiency and cell-cell communication, and modulations of these phenomena by the respective cellular or pathogen ligands.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1267: Sphingolipids - Signal and Disease