SCIENCE:邵峰组发现细胞毒性淋巴细胞诱导细胞焦亡的机制

2020-04-17 MedSci原创 MedSci原创

细胞毒性淋巴细胞介导的免疫依赖于颗粒酶(granzymes)。颗粒酶被认为是通过诱导细胞凋亡来杀死靶细胞的,但是,至今为止,我们对其基本机制还不完全了解。

细胞毒性淋巴细胞介导的免疫依赖于颗粒酶(granzymes)。颗粒酶被认为是通过诱导细胞凋亡来杀死靶细胞的,但是,至今为止,我们对其基本机制还不完全了解。

最近,邵峰课题组报告了自然杀伤细胞和细胞毒性T淋巴细胞通过焦亡杀伤gasdermin B (GSDMB)阳性细胞,这是gasdermin家族孔洞形成蛋白造成的一种促炎性细胞死亡形式。

GSDMB被淋巴细胞源性粒细胞酶A(GZMA)裂解,释放出孔形成蛋白的活性,从而产生杀伤力。

干扰素γ可上调GSDMB的表达,促进脓毒症的发生。

GSDMB在某些组织中高度表达,特别是消化道上皮细胞,包括衍生肿瘤等。将可被GZMA切割的GSDMB引入小鼠癌细胞中,可促进小鼠肿瘤清除。

本研究确定了gasdermin介导的脓毒症是一种细胞毒性淋巴细胞杀伤机制,可能会提高抗肿瘤免疫力。

 

原始出处:

Zhiwei Zhou et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. SCIENCE, 2020. DOI: 10.1126/science.aaz7548

 

 

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    2020-04-19 jichang
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    2020-04-17 肿肿

    机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要

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