Response of Epidermolysis Bullosa Fibroblasts to Factors Derived From Macrophages and Polymorphonuclear Leukocytes in Terms of Collagenase Production

Clinical Criteria for Differentiating between Recessive and Dominant Forms of Dystrophic Epidermolysis Bullosa, Elaborated from an Analysis of 119 Cases

“…Bauer et al (30) suggested that collagenase overexpression was of pathologic importance and a specific biochemical marker of RDEB cells, because the other inherited forms of EB including DDEB, did not display this abnormality. We have demonstrated that RDEB fibroblasts, but not DDEB fibroblasts, showed altered responses to interleukin-l and macrophage/polymorphonuclear leukocyte factors in terms of collagenase synthesis (31,32). In addition, we demonstrated that gene expression of stromelysin, a member of the metalloproteinase family, was increased in RDEB, but not in DDEB fibroblasts (33).…”

Long-Term Follow-Up of Amniotic Membrane Graft for the Treatment of Symblepharon in a Patient With Recessive Dystrophic Epidermolysis Bullosa

“…9,10 In vitro studies suggest an increase in collagenase production by RDEB fibroblasts in the presence of inflammatory cells, which leads to further collagen breakdown. 11 The presence of inflammatory mediators may explain why our patient developed corneal haze on both attempts to completely taper FML. We have maintained our patient on once daily dosing of FML.…”

Rapid generation of Col7a1−/− mouse model of recessive dystrophic epidermolysis bullosa and partial rescue via immunosuppressive dermal mesenchymal stem cells

“…Although T cell immunosuppressive capacity is not germane to the NSG model, evidence indicates that PD-1 engagement with PD-L1 displayed by macrophages (and present in NSG animals) induces a regulatory profile characterized by activation of TLR4 downstream MAPK signaling pathways and resulting in a decrease in inflammatory mediators and production of anti-inflammatory cytokines. 28 Moreover, fibroblasts in RDEB have long been known to be abnormally sensitive to macrophage-derived factors with regard to collagenase production involved in lesion evolution and severity 29 While these pathogenic observations and related speculation are preliminary, and require confirmation and mechanistic validation, they provide proof-of-principle for further studies deploying human immunomodulatory cells in this novel NSG RDEB model system. In particular, although murine ABCB5+ cells have been demonstrated to home to skin, 24 we were unable to document the presence of human ABCB5+ cells at the timepoints examined in this study.…”