Perforin-mediated target-cell death and immune homeostasis

被引:473
作者
Voskoboinik, Ilia
Smyth, Mark J.
Trapani, Joseph A.
机构
[1] Peter MacCallum Canc Ctr, Canc Immunol Program, Melbourne, Vic 3002, Australia
[2] Univ Melbourne, Dept Genet, Parkville, Vic 3010, Australia
[3] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia
基金
英国医学研究理事会;
关键词
D O I
10.1038/nri1983
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The granule exocytosis pathway of cytotoxic lymphocytes is crucial for immune surveillance and homeostasis. The trafficking of granule components, including the membrane-disruptive protein perforin, to the immunological synapse leads to the delivery of granule proteases (granzymes) into the target cell and its destruction through apoptosis. Several independent molecular abnormalities associated with defects of either granule trafficking or perforin function can cause cytotoxic lymphocyte dysfunction. In humans, inherited perforin mutations result in severe immune dysregulation that manifests as familial haemophagocytic lymphohistiocytosis. This Review describes recent progress in defining the structure, function, biochemistry and cell biology of perforin.
引用
收藏
页码:940 / 952
页数:13
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