炎症和风湿病中的颗粒酶丝氨酸蛋白酶

IF 29.4 1区 医学 Q1 RHEUMATOLOGY Nature Reviews Rheumatology Pub Date : 2024-04-30 DOI:10.1038/s41584-024-01109-5
Alexandre Aubert, Karen Jung, Sho Hiroyasu, Julian Pardo, David J. Granville
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引用次数: 0

摘要

颗粒酶(颗粒分泌酶)是丝氨酸蛋白酶的一个家族,自 30 多年前被发现以来,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,与孔形成蛋白穿孔素合作,通过免疫突触传递到靶细胞的细胞质中。内化后,颗粒酶可通过裂解细胞内底物导致细胞死亡。不过,现在也有证据表明,颗粒酶还具有非细胞毒性、促炎症、细胞内和细胞外的特异功能。在病理条件下,免疫细胞和非免疫细胞都能产生和分泌颗粒酶。颗粒酶在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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Granzyme serine proteases in inflammation and rheumatic diseases
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. Granzyme serine proteases are known for their perforin-dependent cytotoxic activities, but evidence also indicates that they have a range of non-cytotoxic, pro-inflammatory intracellular and extracellular functions. In this Review, the authors discuss granzyme biology with an emphasis on its involvement in rheumatic disease pathology.
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来源期刊
Nature Reviews Rheumatology
Nature Reviews Rheumatology 医学-风湿病学
CiteScore
29.90
自引率
0.90%
发文量
137
审稿时长
6-12 weeks
期刊介绍: Nature Reviews Rheumatology is part of the Nature Reviews portfolio of journals. The journal scope covers the entire spectrum of rheumatology research. We ensure that our articles are accessible to the widest possible audience.
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