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

Dendritic cells (DCs) play a central role in the initiation and regulation of the immune response. The modalities by which Dcs are committed to underg o apoptosis are poorly defined. Here it is shown that, unlike death recepto r 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-i nduced Delta Psim dissipation. Importantly, mature DCs (MDCs) displayed rel ative resistance to UVB; UVB-induced caspase activation and apoptosis were substantially delayed compared to immature DCs (IDCs), Resistance correlate d with the strong upregulation of cellular FLIP and bcl2 observed in MDCs c ompared to IDCs,(Blood, 2001;97:1803-1808) (C) 2001 by The American Society of Hematology.