The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury.
The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury.
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DOI：
10.3389/fimmu.2018.00407
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发表时间：
2018
影响因子：
7.3
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Fang H;Zhang Y;Li N;Wang G;Liu Z
大疱性类天疱疮（BP）是一种自身免疫性和炎症性皮肤病，与表皮下水疱和针对半桥粒组分BP 180和BP 230的自身抗体相关。通过被动地将抗BP180 IgG转移到小鼠中来开发BP的动物模型，其概括了人BP的关键特征。通过使用这些体内模型系统，鉴定了导致BP疾病表型的关键细胞和分子事件，包括致病性IgG与其靶标的结合、经典途径的补体激活、肥大细胞脱粒以及嗜中性粒细胞的浸润和激活。由浸润的中性粒细胞释放的蛋白酶切割BP180和其他半桥粒相关蛋白，引起DEJ分离。肥大细胞和肥大细胞衍生的介质，包括炎性细胞因子和蛋白酶增加，在病变的皮肤和水疱液的BP。BP动物模型的证据也暗示肥大细胞在BP的发病机制。然而，最近的研究质疑肥大细胞在自身免疫性疾病，如多发性硬化症，类风湿性关节炎和获得性大疱性表皮病中的致病作用。本文综述了BP病理生理学的现有知识，重点是肥大细胞在BP中的潜在作用以及未来需要解决的与肥大细胞相关的关键问题。
Bullous pemphigoid (BP) is an autoimmune and inflammatory skin disease associated with subepidermal blistering and autoantibodies directed against the hemidesmosomal components BP180 and BP230. Animal models of BP were developed by passively transferring anti-BP180 IgG into mice, which recapitulates the key features of human BP. By using these in vivo model systems, key cellular and molecular events leading to the BP disease phenotype are identified, including binding of pathogenic IgG to its target, complement activation of the classical pathway, mast cell degranulation, and infiltration and activation of neutrophils. Proteinases released by infiltrating neutrophils cleave BP180 and other hemidesmosome-associated proteins, causing DEJ separation. Mast cells and mast cell-derived mediators including inflammatory cytokines and proteases are increased in lesional skin and blister fluids of BP. BP animal model evidence also implicates mast cells in the pathogenesis of BP. However, recent studies questioned the pathogenic role of mast cells in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and epidermolysis bullosa acquisita. This review highlights the current knowledge on BP pathophysiology with a focus on a potential role for mast cells in BP and mast cell-related critical issues needing to be addressed in the future.