Turner Christopher T
Future Industries Institute, University of South Australia, Adelaide, SA, Australia.
Front Immunol. 2025 Jun 18;16:1620670. doi: 10.3389/fimmu.2025.1620670. eCollection 2025.
Granzyme K (GzmK) is an immune-secreted serine protease typically expressed at low levels but elevated in response to tissue injury and disease. Known as an orphan granzyme due to limited scientific investigation, this tryptase is being redefined as having important roles in inflammation and disease pathogenesis. Multiple GzmK expressing CD8 T cell subsets are being identified with augmented expression and important roles in disease. Traditionally recognized as a mediator of cytotoxic lymphocyte-mediated cell death, GzmK's role is being recharacterized through multiple recently released studies focused on newly identified extracellular mechanisms of action. These studies identify GzmK to be inflammatory, being able to trigger pro-inflammatory cytokine release, enhance immune cell recruitment, exacerbate the immune response to bacterial infections, and activate complement. In multiple disease states, dysregulated GzmK expression and potential accumulation in the extracellular space directly contributes to impaired health outcomes, thereby suggesting downregulation may prevent disease severity. GzmK is therefore emerging as a therapeutic target, potentially valuable in sepsis, pulmonary disease, inflammatory skin disease, rheumatoid arthritis and even aging.
颗粒酶K（GzmK）是一种免疫分泌的丝氨酸蛋白酶，通常表达水平较低，但在组织损伤和疾病反应中会升高。由于科学研究有限，这种类胰蛋白酶被称为孤儿颗粒酶，目前正被重新定义为在炎症和疾病发病机制中具有重要作用。多个表达GzmK的CD8 T细胞亚群被识别出来，其表达增加且在疾病中发挥重要作用。传统上认为GzmK是细胞毒性淋巴细胞介导的细胞死亡的介质，最近多项研究聚焦于新发现的细胞外作用机制，对其作用进行了重新描述。这些研究表明GzmK具有炎症性，能够触发促炎细胞因子释放、增强免疫细胞募集、加剧对细菌感染的免疫反应并激活补体。在多种疾病状态下，GzmK表达失调以及在细胞外空间的潜在积累直接导致健康状况受损，因此提示下调其表达可能预防疾病严重程度。因此，GzmK正成为一个治疗靶点，在脓毒症、肺部疾病、炎症性皮肤病、类风湿性关节炎甚至衰老方面可能具有重要价值。
