Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, United States.
University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States.
Front Immunol. 2024 Jun 20;15:1422113. doi: 10.3389/fimmu.2024.1422113. eCollection 2024.
Recent breakthroughs in discovering novel immune signaling pathways have revolutionized different disease treatments. SERPINB9 (Sb9), also known as Proteinase Inhibitor 9 (PI-9), is a well-known endogenous inhibitor of Granzyme B (GzmB). GzmB is a potent cytotoxic molecule secreted by cytotoxic T lymphocytes and natural killer cells, which plays a crucial role in inducing apoptosis in target cells during immune responses. Sb9 acts as a protective mechanism against the potentially harmful effects of GzmB within the cells of the immune system itself. On the other hand, overexpression of Sb9 is an important mechanism of immune evasion in diseases like cancers and viral infections. The intricate functions of Sb9 in different cell types represent a fine-tuned regulatory mechanism for preventing immunopathology, protection against autoimmune diseases, and the regulation of cell death, all of which are essential for maintaining health and responding effectively to disease challenges. Dysregulation of the Sb9 will disrupt human normal physiological condition, potentially leading to a range of diseases, including cancers, inflammatory conditions, viral infections or other pathological disorders. Deepening our understanding of the role of Sb9 will aid in the discovery of innovative and effective treatments for various medical conditions. Therefore, the objective of this review is to consolidate current knowledge regarding the biological role of Sb9. It aims to offer insights into its discovery, structure, functions, distribution, its association with various diseases, and the potential of nanoparticle-based therapies targeting Sb9.
最近在发现新型免疫信号通路方面的突破,彻底改变了各种疾病的治疗方法。丝氨酸蛋白酶抑制剂 B9(Sb9),也称为蛋白酶抑制剂 9(PI-9),是 Granzyme B(GzmB)的一种知名内源性抑制剂。GzmB 是细胞毒性 T 淋巴细胞和自然杀伤细胞分泌的一种强效细胞毒性分子,在免疫反应中对靶细胞的凋亡起着至关重要的作用。Sb9 作为一种保护机制,可防止 GzmB 在免疫系统自身细胞内产生潜在的有害影响。另一方面,Sb9 的过度表达是癌症和病毒感染等疾病中免疫逃逸的重要机制。Sb9 在不同细胞类型中的复杂功能代表了一种精细的调节机制,可防止免疫病理学、预防自身免疫性疾病以及调节细胞死亡,所有这些对于维持健康和对疾病挑战做出有效反应都是至关重要的。Sb9 的失调会破坏人体的正常生理状态,可能导致一系列疾病,包括癌症、炎症、病毒感染或其他病理紊乱。深入了解 Sb9 的作用将有助于发现各种医疗条件的创新和有效治疗方法。因此,本综述的目的是整合关于 Sb9 的生物学作用的现有知识。它旨在深入了解其发现、结构、功能、分布、与各种疾病的关联,以及针对 Sb9 的基于纳米颗粒的治疗方法的潜力。