CD137 Panaxadiol ligand signaling can also induce maturation of human immature monocyte-derived DCs leading to an enhanced expression of costimulatory molecules, IL-12 secretion, and an enhanced capacity of the DCs to stimulate T cell proliferation, IFN-c secretion and in vivo migration towards a CCL19 gradient. Two recent studies report that CD137 ligand signaling induces full human monocyte to DC differentiation. CD137 ligand signaling triggered by a monoclonal anti-CD137 ligand antibody and complemented by IL-4 induced costimulatory molecule expression and T cell stimulatory activity. However, recombinant CD137 protein as a sole factor is sufficient to induce human monocyte to DC differentiation and these CD137L-DCs are more potent than classical DCs in inducing proliferation, IFNc secretion and perforin expression by T cells. These data Fenoprofen Calcium indicate that CD137L-DCs may also be more potent in inducing protective T cell responses than classical DCs. However, a reliable conclusion about the potency of the different DC populations should be based on in vivo experiments. As these would be most easily performed in mice we tested whether CD137 ligand signaling also induces DC differentiation in murine monocytes, so that murine CD137L-DCs can be tested for their ability to induce anti-pathogen and anti-tumor immune responses in vivo. Just as in human monocytes CD137 ligand signaling induced attachment, morphological changes and proliferation in murine monocytes. However, neither monocyte to DC differentiation nor maturation of immature DCs was induced in the murine system pointing to a species difference in the effects of CD137 ligand signaling between human and murine monocytes. Epidermolysis bullosa simplex is an inherited skinblistering disease that is characterized by the appearance of fluid-filled blisters after mild mechanical trauma. Blistering arises from rupturing of the keratinocytes of the epidermal stratum basale and is most often attributed to dominant genetic mutations in the genes for keratin K5 or K14 proteins. The clinical severity of the EBS phenotype varies from mild to severe and is determined in part by the position of the mutation in the K5 or K14 genes. In severe cases of EBS, a diagnosis is confirmed by the detection of an intraepidermal cleavage in the stratum basale using immunohistochemistry or electron microscopy. In addition, basal keratinocytes within EBSDM patients typically possess numerous aggregates in the cytoplasm formed by non-filamentous keratin protein. Mutations associated with the EBS-DM type are typically found in the highly conserved boundary regions of the central a-helical rod domains of keratin proteins; these boundary motifs are particularly important in filament assembly. The most commonly altered amino acid residue is the arginine at position 125 of K14, which accounts for 70% of all EBS-DM cases. Genetic studies of EBS patients as well as experiments with transgenic cells and mice provide compelling evidence for a causal link between mutations in K5/K14 genes and EBS, although the exact biophysical mechanism of basal keratinocyte fragility in EBS patients remains unknown. Several hypotheses have been proposed in the literature to explain the mechanical fragility of EBS keratinocytes.