Reconstitution with WT ISG15 and inhibition of apoptosis rescue apoptosis of IFNα-treated ISG15 KO cells. (A) Healing/migration ability of WT, UBE1L KO, and ISG15 KO fibroblasts, as well as ISG15 KO cells complemented with WT ISG15 or Luc, was assessed with the scratch assay for 93 h. (B) Apoptosis following 72-h IFNα2b treatment of WT, UBE1L KO, and ISG15 KO fibroblasts, as well as ISG15 KO cells complemented with WT ISG15 or Luc, was assessed by quantifying cleaved caspase 3 levels through flow cytometry. (C) Rescue of A549 ISG15 KO IFNα2b-induced cell death with pan-caspase inhibitor (Z-VAD). (D) Proliferation of ISG15 KO lung epithelial cells (A549) with or without IFNα2b as compared to control. (E) CASP3 IHC for three healthy volunteer and three patient’s skin biopsies. White arrows indicate areas of cleaved Caspase-3 (brown).