In vitro and in vivo models to investigate the pathomechanisms and novel treatments for pemphigoid diseases

被引:41
作者
Bieber, Katja [1 ]
Koga, Hiroshi [2 ]
Nishie, Wataru [3 ]
机构
[1] Univ Lubeck, Lubeck Inst Expt Dermatol, Lubeck, Germany
[2] Kurume Univ, Dept Dermatol, Sch Med, Fukuoka, Japan
[3] Hokkaido Univ, Dept Dermatol, Grad Sch Med, Sapporo, Hokkaido, Japan
关键词
animal model; autoimmune bullous dermatoses; autoimmunity; bullous pemphigoid; epidermolysis bullosa acquisita; pemphigoid disease; skin; EPIDERMOLYSIS-BULLOSA ACQUISITA; INDUCE SUBEPIDERMAL BLISTERS; VII-COLLAGEN ANTIBODIES; ACTIVE-MOUSE MODEL; PASSIVE TRANSFER; AUTOIMMUNE-DISEASE; COMPLEMENT ACTIVATION; CUTANEOUS INFLAMMATION; ANIMAL-MODELS; NEONATAL MICE;
D O I
10.1111/exd.13415
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Pemphigoid diseases (PD) are a subgroup of rare acute or chronic autoimmune skin disorders characterized and caused by autoantibodies directed against distinct structural components of the dermal-epidermal junction. Binding of autoantibodies to their targets leads to the formation of blisters and erosions in patients. PDs comprise eight disorders for which the molecular target antigens have been identified. First, we review the available in vitro and ex vivo models for analysis of distinct aspects of the pathogenesis of PDs. This includes the binding of autoantibodies to skin sections, the analysis of blister formation capability and skin complement activation as well as investigation of neutrophil and keratinocyte activation. In addition to this, several animal models of PD have been developed during the last decades. These animal models have greatly contributed to our current understanding of the pathogenesis of PDs. We summarize spontaneously arising PD in animals and the induction of PD by transfer of (auto) antibodies, transfer of (auto)-antigen-specific lymphocytes and by immunization. In combined use, these models allow dissecting all aspects of PD pathogenesis, for example loss of tolerance, autoantibody production and inflammatory skin processes that lead to blister formation. Overall, we aimed to foster translational biomedical research, to deepen our understanding of PD pathogenesis and to develop novel treatments for patients suffering from these life-threatening and difficult-to-treat autoimmune diseases.
引用
收藏
页码:1163 / 1170
页数:8
相关论文
共 69 条
[41]   Signalling and targeted therapy of inflammatory cells in epidermolysis bullosa acquisita [J].
Ludwig, Ralf J. .
EXPERIMENTAL DERMATOLOGY, 2017, 26 (12) :1179-1186
[42]   Mechanisms of Autoantibody-Induced Pathology [J].
Ludwig, Ralf J. ;
Vanhoorelbeke, Karen ;
Leypoldt, Frank ;
Kaya, Ziya ;
Bieber, Katja ;
McLachlan, Sandra M. ;
Komorowski, Lars ;
Luo, Jie ;
Cabral-Marques, Otavio ;
Hammers, Christoph M. ;
Lindstrom, Jon M. ;
Lamprecht, Peter ;
Fischer, Andrea ;
Riemekasten, Gabriela ;
Tersteeg, Claudia ;
Sondermann, Peter ;
Rapoport, Basil ;
Wandinger, Klaus-Peter ;
Probst, Christian ;
El Beidaq, Asmaa ;
Schmidt, Enno ;
Verkman, Alan ;
Manz, Rudolf A. ;
Nimmerjahn, Falk .
FRONTIERS IN IMMUNOLOGY, 2017, 8
[43]   Generation of Antibodies of Distinct Subclasses and Specificity Is Linked to H2s in an Active Mouse Model of Epidermolysis Bullosa Acquisita [J].
Ludwig, Ralf J. ;
Recke, Andreas ;
Bieber, Katja ;
Mueller, Susen ;
Marques, Andreia de Castro ;
Banczyk, David ;
Hirose, Misa ;
Kasperkiewicz, Michael ;
Ishii, Norito ;
Schmidt, Enno ;
Westermann, Juergen ;
Zillikens, Detlef ;
Ibrahim, Saleh M. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2011, 131 (01) :167-176
[44]   The alternative pathway of complement activation is critical for blister induction in experimental epidermolysis bullosa acquisita [J].
Mihai, Sidonia ;
Chiriac, Mircea T. ;
Takahashi, Kazue ;
Thurman, Joshua M. ;
Holers, V. Michael ;
Zillikens, Detlef ;
Botto, Marina ;
Sitaru, Cassian .
JOURNAL OF IMMUNOLOGY, 2007, 178 (10) :6514-6521
[45]  
NAPARSTEK Y, 1993, ANNU REV IMMUNOL, V11, P79, DOI 10.1146/annurev.iy.11.040193.000455
[46]   Antibodies to Pathogenic Epitopes or Type XVII Collagen Cause Skin Fragility in a Complement-Dependent and -Independent Manner [J].
Natsuga, Ken ;
Nishie, Wataru ;
Shinkuma, Satoru ;
Ujiie, Hideyuki ;
Nishimura, Machiko ;
Sawamura, Daisuke ;
Shimizu, Hiroshi .
JOURNAL OF IMMUNOLOGY, 2012, 188 (11) :5792-5799
[47]   Humanization of autoantigen [J].
Nishie, Wataru ;
Sawamura, Daisuke ;
Goto, Maki ;
Ito, Kei ;
Shibaki, Akihiko ;
McMillan, James R. ;
Sakai, Kaori ;
Nakamura, Hideki ;
Olasz, Edit ;
Yancey, Kim B. ;
Akiyama, Masashi ;
Shimizu, Hiroshi .
NATURE MEDICINE, 2007, 13 (03) :378-383
[48]   Update on the pathogenesis of bullous pemphigoid: An autoantibody-mediated blistering disease targeting collagen XVII [J].
Nishie, Wataru .
JOURNAL OF DERMATOLOGICAL SCIENCE, 2014, 73 (03) :179-186
[49]   Human bullous pemphigoid antigen 2 transgenic skin elicits specific IgG in wild-type mice [J].
Olasz, Edit B. ;
Roh, Jooyoung ;
Yee, Carole L. ;
Arita, Ken ;
Akiyama, Masashi ;
Shimizu, Hiroshi ;
Vogel, Jonathan C. ;
Yancey, Kim B. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2007, 127 (12) :2807-2817
[50]   The Flavonoid Luteolin Inhibits Fcγ-Dependent Respiratory Burst in Granulocytes, but Not Skin Blistering in a New Model of Pemphigoid in Adult Mice [J].
Oswald, Eva ;
Sesarman, Alina ;
Franzke, Claus-Werner ;
Woelfle, Ute ;
Bruckner-Tuderman, Leena ;
Jakob, Thilo ;
Martin, Stefan F. ;
Sitaru, Cassian .
PLOS ONE, 2012, 7 (02)