人皮肤器官培养模型作为小鼠天疱疮模型的最佳补充工具。

IF 1.3 4区 农林科学 Q2 VETERINARY SCIENCES
Veronika Hartmann, William Vj Hariton, Siavash Rahimi, Christoph M Hammers, Ralf J Ludwig, Eliane J Müller, Jennifer E Hundt
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引用次数: 1

摘要

天疱疮是一种严重的皮肤和/或粘膜自身免疫性大疱性疾病,由自身抗体引起,主要针对粘附蛋白粘粒蛋白(Dsg) 3和/或Dsg1。临床上,天疱疮的特点是松弛起泡,导致严重的水和电解质流失。在引入皮质类固醇治疗之前,这种疾病在许多情况下是致命的。尽管最近的治疗进步,天疱疮患者的治疗集中在长期的全身免疫抑制和仍然具有挑战性。目前天疱疮的药物开发主要集中在致病的B细胞和自身抗体上,最近也在调节自身抗体诱导的组织病理和角质细胞信号传导上。这种药物的开发需要可靠的临床前模型系统来复制人类疾病的发病机制。其中包括基于Dsg3、Dsg1/3或dsg1特异性自身抗体转移的新生和成年小鼠模型。为了减少动物实验的数量,我们最近建立了标准化的天疱疮人皮肤器官培养(HSOC)模型。该模型再现了寻常型天疱疮自身抗体诱导的组织病理的临床表型。为了诱导起泡,将靶向Dsg1和3的重组单链可变片段(scFv)注射到人体皮肤中(从整形手术中获得)。HSOC模型的进一步表征表明,天疱疮的关键形态学、分子和免疫学特征正在被复制。因此,天疱疮HSOC模型是基于(自身)抗体转移的天疱疮动物模型系统的一个很好的替代方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The human skin organ culture model as an optimal complementary tool for murine pemphigus models.

Pemphigus is a severe autoimmune bullous disease of the skin and/or mucous membranes caused by autoantibodies that mainly target the adhesion proteins desmoglein (Dsg) 3 and/or Dsg1. Clinically, pemphigus is characterized by flaccid blistering, leading to severe water and electrolyte loss. Before the introduction of corticosteroid treatment, the disease turned out to be fatal in many cases. Despite recent therapeutic improvements, treatment of pemphigus patients is centred on prolonged systemic immunosuppression and remains challenging. Current drug development for pemphigus has a strong focus on disease-causing B cells and autoantibodies and, more recently, also on modulating autoantibody-induced tissue pathology and keratinocyte signalling. This drug development requires reliable pre-clinical model systems replicating the pathogenesis of the human disease. Among those are neonatal and adult mouse models based on the transfer of Dsg3, Dsg1/3 or Dsg1-specific autoantibodies. To reduce the number of animal experiments, we recently established a standardized human skin organ culture (HSOC) model for pemphigus. This model reproduces the clinical phenotype of autoantibody-induced tissue pathology in pemphigus vulgaris. For induction of blistering, a recombinant single-chain variable fragment (scFv) targeting both Dsg1 and 3 is injected into pieces of human skin (obtained from plastic surgeries). Further characterization of the HSOC model demonstrated that key morphologic, molecular and immunologic features of pemphigus are being replicated. Thus, the pemphigus HSOC model is an excellent alternative to pemphigus animal model systems that are based on the transfer of (auto)antibodies.

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来源期刊
Laboratory Animals
Laboratory Animals 生物-动物学
CiteScore
4.90
自引率
8.30%
发文量
64
审稿时长
6-12 weeks
期刊介绍: The international journal of laboratory animal science and welfare, Laboratory Animals publishes peer-reviewed original papers and reviews on all aspects of the use of animals in biomedical research. The journal promotes improvements in the welfare or well-being of the animals used, it particularly focuses on research that reduces the number of animals used or which replaces animal models with in vitro alternatives.
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