Establishing a humanized mouse model for Epidermolysis bullosa acquisita (EBA)
VOSS L. 1, ALTMANN L. 1, BIEBER K. 2, LUX A. 1
1 Department of Biology, Chair of Genetics, Friedrich Alexander University Erlangen-Nürnberg, Germany, Erlangen, Germany; 2 Lübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Germany, Lübeck, Germany
Epidermolysis bullosa acquisita (EBA) is an autoimmune skin blistering disease caused by autoantibodies against collagen VII deposited in the dermal-epidermal junction of the skin. In response to activation of Fcγ receptors (FcγRs) by pathogenic IgG, effector mechanisms such as the release of reactive oxygen species are triggered in myeloid effector cells. This results in degradation of the dermal-epidermal adhesion complex, ultimately leading to formation of skin blisters and erosions. While the pathomechanisms of EBA are well-characterized in mice and therapeutic strategies can be investigated in a range of classical mouse models, a gap of knowledge exists concerning the mechanisms in humans. As in vitro assays using human cells cannot reflect the complex in vivo situation, in vivo models using humanized mice are a valuable tool to study disease pathogenesis and the potential of novel therapeutic strategies more closely to the human situation.
The aim is to establish a novel mouse model for EBA featuring a humanized immune system. Following characterization of skin inflammation the model will be employed to examine the potential of selected therapeutic regimens.
Immunodeficient mice are first reconstituted with human stem cells (HSCs) purified from umbilical cord blood. For establishing the disease, anti-ColVII IgG is injected and development of inflammatory skin lesions is determined by clinical scoring. Additionally, inflammatory infiltrates are analyzed by immunohistochemistry and flow cytometry is used to elucidate inflammatory processes.
Results and Conclusion
Upon HSC transplantation, immunodeficient mice develop a human immune system composed of all major leukocyte subsets including expression of human FcγRs. EBA induction by injection of anti-ColVII IgG causes development of skin inflammation in humanized mice which correlated with the infiltration of human immune cells in the tissue. Thus, EBA in humanized mice is a suitable model to further investigate pathomechanisms and efficacy of therapeutic regimens.