DermoLAB, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy.
Hematology Section, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy.
Int J Mol Sci. 2022 Jun 24;23(13):7044. doi: 10.3390/ijms23137044.
Pemphigus is a life-threatening autoimmune disease. Several phenotypic variants are part of this family of bullous disorders. The disease is mainly mediated by pathogenic autoantibodies, but is also directed against two desmosomal adhesion proteins, desmoglein 1 (DSG1) and 3 (DSG3), which are expressed in the skin and mucosae. By binding to their antigens, autoantibodies induce the separation of keratinocytes, in a process known as acantholysis. The two main Pemphigus variants are Pemphigus vulgaris and foliaceus. Several models of Pemphigus have been described: in vitro, ex vivo and in vivo, passive or active mouse models. Although no model is ideal, different models display specific characteristics that are useful for testing different hypotheses regarding the initiation of Pemphigus, or to evaluate the efficacy of experimental therapies. Different disease models also allow us to evaluate the pathogenicity of specific Pemphigus autoantibodies, or to investigate the role of previously not described autoantigens. The aim of this review is to provide an overview of Pemphigus disease models, with the main focus being on active models and their potential to reproduce different disease subgroups, based on the involvement of different autoantigens.
天疱疮是一种危及生命的自身免疫性疾病。该大疱性疾病家族包含多种表型变异体。这种疾病主要由致病性自身抗体介导，但也针对两种桥粒黏附蛋白，即表皮桥粒芯糖蛋白 1（DSG1）和 3（DSG3），它们在皮肤和黏膜中表达。自身抗体与它们的抗原结合，诱导角质形成细胞分离，这一过程称为棘层松解。天疱疮的两种主要变异体是寻常型天疱疮和落叶型天疱疮。已经描述了几种天疱疮模型：体外、离体和体内，被动或主动小鼠模型。尽管没有一种模型是理想的，但不同的模型显示出特定的特征，这些特征可用于测试关于天疱疮发病机制的不同假设，或评估实验治疗的疗效。不同的疾病模型还使我们能够评估特定天疱疮自身抗体的致病性，或研究以前未描述的自身抗原的作用。本文综述的目的是提供天疱疮疾病模型的概述，主要重点是主动模型及其在基于不同自身抗原参与的情况下重现不同疾病亚组的潜力。
