Ontrafelen van de mechanismen nodig om autoreactieve T-cell reactiviteit te onderdrukken tijdens macrofaag-apoptotische beta cel interactie

The efficient removal of apoptotic cells by phagocytes is important for maintaining tolerance to selfantigens. The detection and disposal of apoptotic cells generally promotes a silent response by the phagocytes and thereby also a dampening of potential auto-aggressive T cells. Although under homeostatic conditions the events required for such a quiescent response by the phagocytes are well characterized, it is clear that under inflammatory conditions certain defects in apoptotic cell clearance have been linked to the onset of inflammation and autoimmune disease. Here we aim to characterize the molecular and cellular events that underlie apoptotic beta cell recognition and uptake by macrophages during autoimmune diabetes. We aim on the one hand, to investigate what machinery and sensing molecules for apoptotic cell engulfing are needed by the macrophage. On the other hand we aim to investigate how signals from the stressed or dying beta cell may influence macrophages’ innate responses as well as T cell stimulatory/suppressive capacity. The knowledge acquired by this project could be harnessed for new therapeutic strategies not only in the context of type 1 diabetes but also in a wide range of generic inflammatory and autoimmune diseases.