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Granzyme serine proteases in inflammation and rheumatic diseases
Nature Reviews Rheumatology ( IF 29.4 ) Pub Date : 2024-04-30 , DOI: 10.1038/s41584-024-01109-5
Alexandre Aubert 1 , Karen Jung 1 , Sho Hiroyasu 2 , Julian Pardo 3, 4 , David J Granville 1, 5
Affiliation  

Granzymes (granule-secreted enzymes) are a family of serine proteases that have been viewed as redundant cytotoxic enzymes since their discovery more than 30 years ago. Predominantly produced by cytotoxic lymphocytes and natural killer cells, granzymes are delivered into the cytoplasm of target cells through immunological synapses in cooperation with the pore-forming protein perforin. After internalization, granzymes can initiate cell death through the cleavage of intracellular substrates. However, evidence now also demonstrates the existence of non-cytotoxic, pro-inflammatory, intracellular and extracellular functions that are granzyme specific. Under pathological conditions, granzymes can be produced and secreted extracellularly by immune cells as well as by non-immune cells. Depending on the granzyme, accumulation in the extracellular milieu might contribute to inflammation, tissue injury, impaired wound healing, barrier dysfunction, osteoclastogenesis and/or autoantigen generation.



中文翻译:


粒酶丝氨酸蛋白酶在炎症和风湿性疾病中的作用



颗粒酶(颗粒分泌酶)是丝氨酸蛋白酶家族,自 30 多年前发现以来一直被视为多余的细胞毒性酶。颗粒酶主要由细胞毒性淋巴细胞和自然杀伤细胞产生,通过免疫突触与成孔蛋白穿孔素配合被递送到靶细胞的细胞质中。内化后,颗粒酶可以通过细胞内底物的裂解启动细胞死亡。然而,现在的证据还表明存在颗粒酶特异性的非细胞毒性、促炎性、细胞内和细胞外功能。在病理条件下,颗粒酶可以由免疫细胞以及非免疫细胞产生并分泌到细胞外。根据颗粒酶的不同,细胞外环境中的积累可能会导致炎症、组织损伤、伤口愈合受损、屏障功能障碍、破骨细胞生成和/或自身抗原生成。

更新日期:2024-04-30
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