UVB-induced apoptosis of human dendritic cells: contribution by caspase-dependent and caspase-independent pathway

Dendritic cells (DCs) play a central role in the initiation and regulation of the immune response. The modalities by which Dcs are committed to undergo apoptosis are poorly defined. Here it is shown that, unlike death receptor ligands, UVB radiation triggers apoptosis of human DCs very efficiently. UVB exposure is followed by the activation of caspases 8, 9, and 3, by the loss of mitochondrial transmembrane potential (Delta Psim), and by cellular and nuclear fragmentation, Caspase inhibitors substantially prevented the occurrence of cellular;and nuclear fragmentation but had no effect on UVB-induced Delta Psim dissipation. Importantly, mature DCs (MDCs) displayed relative resistance to UVB; UVB-induced caspase activation and apoptosis were substantially delayed compared to immature DCs (IDCs), Resistance correlated with the strong upregulation of cellular FLIP and bcl2 observed in MDCs compared to IDCs