邵峰團隊發現觸發細胞焦亡的新途徑
作者：
小柯機器人發布時間：2020/4/18 14:29:59
近日，北京生命科學研究所邵峰團隊發現，細胞毒性淋巴細胞來源的顆粒酶A切割GSDMB從而觸發靶細胞焦亡。2020年4月16日，《科學》雜誌在線發表了這項成果。
研究人員發現，自然殺傷細胞和細胞毒性T淋巴細胞通過細胞焦亡殺死gasdermin B（GSDMB）陽性細胞。細胞焦亡是打孔蛋白gasdermin家族介導的促炎性細胞死亡形式。殺傷作用是由淋巴細胞來源的顆粒酶A（GZMA）切割GSDMB產生的，從而釋放了其打孔活性。
幹擾素γ上調GSDMB表達並促進細胞焦亡。GSDMB在某些組織，尤其是消化道上皮，包括衍生的腫瘤中高度表達。將GZMA可切割的GSDMB導入鼠類癌細胞可促進小鼠體內的腫瘤清除。
這項研究表明，gasdermin介導的細胞焦亡是一種細胞毒性淋巴細胞殺傷機制，可以增強抗腫瘤免疫。
據了解，細胞毒性淋巴細胞介導的免疫依賴於顆粒酶。儘管尚不完全了解其潛在機制，但人們認為顆粒酶可通過誘導細胞凋亡殺死靶細胞。
附：英文原文
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
Science：《科學》，創刊於1880年。隸屬於美國科學促進會，最新IF：41.037