title: Radiosensitive Hematopoietic Cells Determine the Extent of Skin Inflammation in Experimental Epidermolysis Bullosa Acquisita.
abstract: Animal models have enhanced our understanding of the pathogenesis of autoimmune diseases. For these models, genetically identical, inbred mice have commonly been used. Different inbred mouse strains, however, show a high variability in disease manifestation. Identifying the factors that influence this disease variability could provide unrecognized insights into pathogenesis. We established a novel Ab transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune disease characterized by (muco)-cutaneous blistering caused by anti-type VII collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against the von Willebrand factor A-like domain 2) transfer showed clear variability among inbred mouse strains, that is, severe cutaneous blistering and inflammation in C57BL/6J and absence of skin lesions in MRL/MpJ mice. The transfer of anti-COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex activation of neutrophils from C57BL/6J or MRL/MpJ mice showed an impaired reactive oxygen species release from the latter, whereas no differences were observed after PMA activation. This finding was paralleled by divergent expression profiles of immune complex-activated neutrophils from either C57BL/6J or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine the varying extent of skin inflammation and blistering in the end-stage effector phase of EBA.
authors.affiliation: Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany;
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, D-23538 Lübeck, Germany;
authors.forename: Mareike
authors.initials: M
authors.lastname: Witte
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, D-23538 Lübeck, Germany;
authors.forename: Unni Krishna S R L
authors.initials: UK
authors.lastname: Samavedam
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, D-23538 Lübeck, Germany;
authors.forename: Yask
authors.initials: Y
authors.lastname: Gupta
authors.affiliation: First Department of Dermatology, School of Medicine, Faculty of Medicine Toho University, Tokyo 143-8540, Japan;
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: First Department of Dermatology, School of Medicine, Faculty of Medicine Toho University, Tokyo 143-8540, Japan;
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiko
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, D-23538 Lübeck, Germany;
authors.forename: Tobias
authors.initials: T
authors.lastname: Schröder
authors.affiliation: Department of Chemistry, University of Lübeck, D-23538 Lübeck, Germany; and.
authors.forename: Karsten
authors.initials: K
authors.lastname: Seeger
authors.affiliation: Department of Radiation Oncology, University of Lübeck, D-23538 Lübeck, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Dahlke
authors.affiliation: Department of Radiation Oncology, University of Lübeck, D-23538 Lübeck, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Rades
authors.affiliation: Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany; Lübeck Institute of Experimental Dermatology, University of Lübeck, D-23538 Lübeck, Germany;
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.affiliation: Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany; Lübeck Institute of Experimental Dermatology, University of Lübeck, D-23538 Lübeck, Germany; ralf.ludwig@uksh.de.
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001768:Blister / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000528:radiation effects; D016026:Bone Marrow Transplantation / Q000379:methods*; D024143:Collagen Type VII / Q000276:immunology; D003872:Dermatitis / Q000276:immunology*; D004195:Disease Models, Animal; D016107:Epidermolysis Bullosa Acquisita / Q000276:immunology*; D053263:Gene Regulatory Networks / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D013045:Species Specificity; D059467:Transcriptome / Q000276:immunology
chemical_list: D001323:Autoantibodies; D024143:Collagen Type VII; D007074:Immunoglobulin G; D017382:Reactive Oxygen Species