近日，北京生命科学研究所邵峰团队发现，细胞毒性淋巴细胞来源的颗粒酶A切割GSDMB从而触发靶细胞焦亡。2020年4月16日，《科学》杂志在线发表了这项成果。

Title: Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells

Author: Zhiwei Zhou, Huabin He, Kun Wang, Xuyan Shi, Yupeng Wang, Ya Su, Yao Wang, Da Li, Wang Liu, Yongliang Zhang, Lianjun Shen, Weidong Han, Lin Shen, Jingjin Ding, Feng Shao

Issue&Volume: 2020/04/16

Abstract: Abstract Cytotoxic lymphocyte-mediated immunity relies on granzymes. Granzymes are thought to kill target cells by inducing apoptosis, though the underlying mechanisms are not fully understood. Here, we report that natural killer cells and cytotoxic T lymphocytes kill gasdermin B (GSDMB)–positive cells through pyroptosis, a form of proinflammatory cell death executed by the gasdermin family of pore-forming proteins. Killing results from the cleavage of GSDMB by lymphocyte-derived granzyme A (GZMA), which unleashes its pore-forming activity. Interferon gamma up-regulates GSDMB expression and promotes pyroptosis. GSDMB is highly expressed in certain tissues, particularly digestive tract epithelia including derived tumors. Introducing GZMA-cleavable GSDMB into murine cancer cells promotes tumor clearance in mice. This study establishes gasdermin-mediated pyroptosis as a cytotoxic lymphocyte killing mechanism, which may enhance antitumor immunity.

DOI: 10.1126/science.aaz7548

Source: https://science.sciencemag.org/content/early/2020/04/15/science.aaz7548