British Columbia Professional Firefighters' Burn and Wound Healing Laboratory, International Collaboration On Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z7, Canada.
Biomolecules. 2023 Feb 18;13(2):388. doi: 10.3390/biom13020388.
Autoimmune diseases often present with cutaneous symptoms that contribute to dysfunction, disfigurement, and in many cases, reduced quality-of-life. Unfortunately, treatment options for many autoimmune skin diseases are limited. Local and systemic corticosteroids remain the current standard-of-care but are associated with significant adverse effects. Hence, there is an unmet need for novel therapies that block molecular drivers of disease in a local and/or targeted manner. Granzyme B (GzmB) is a serine protease with known cytotoxic activity and emerging extracellular functions, including the cleavage of cell-cell junctions, basement membranes, cell receptors, and other structural proteins. While minimal to absent in healthy skin, GzmB is markedly elevated in alopecia areata, interface dermatitis, pemphigoid disease, psoriasis, systemic sclerosis, and vitiligo. This review will discuss the role of GzmB in immunity, blistering, apoptosis, and barrier dysfunction in the context of autoimmune skin disease. GzmB plays a causal role in the development of pemphigoid disease and carries diagnostic and prognostic significance in cutaneous lupus erythematosus, vitiligo, and alopecia areata. Taken together, these data support GzmB as a promising therapeutic target for autoimmune skin diseases impacted by impaired barrier function, inflammation, and/or blistering.
自身免疫性疾病常伴有皮肤症状，这些症状导致功能障碍、毁容，在许多情况下还降低了生活质量。不幸的是，许多自身免疫性皮肤病的治疗选择有限。局部和全身皮质类固醇仍然是目前的标准治疗方法，但它们与显著的不良反应有关。因此，迫切需要新的治疗方法，以局部和/或靶向的方式阻断疾病的分子驱动因素。颗粒酶 B（GzmB）是一种丝氨酸蛋白酶，具有已知的细胞毒性活性和新兴的细胞外功能，包括细胞-细胞连接、基底膜、细胞受体和其他结构蛋白的切割。GzmB 在健康皮肤中含量很少或不存在，但在斑秃、界面性皮炎、大疱性类天疱疮、银屑病、系统性硬皮病和白癜风中明显升高。这篇综述将讨论 GzmB 在免疫、大疱、细胞凋亡和自身免疫性皮肤病中屏障功能障碍中的作用。GzmB 在大疱性类天疱疮的发病机制中起因果作用，并在皮肤红斑狼疮、白癜风和斑秃中具有诊断和预后意义。综上所述，这些数据支持 GzmB 作为一种有前途的治疗靶点，可用于受屏障功能障碍、炎症和/或大疱影响的自身免疫性皮肤病。
