The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation

NK 细胞颗粒蛋白 NKG7 调节细胞毒性颗粒的胞吐和炎症

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作者:Susanna S Ng, Fabian De Labastida Rivera, Juming Yan, Dillon Corvino, Indrajit Das, Ping Zhang, Rachel Kuns, Shashi Bhushan Chauhan, Jiajie Hou, Xian-Yang Li, Teija C M Frame, Benjamin A McEnroe, Eilish Moore, Jinrui Na, Jessica A Engel, Megan S F Soon, Bhawana Singh, Andrew J Kueh, Marco J Herold, 

Abstract

Immune-modulating therapies have revolutionized the treatment of chronic diseases, particularly cancer. However, their success is restricted and there is a need to identify new therapeutic targets. Here, we show that natural killer cell granule protein 7 (NKG7) is a regulator of lymphocyte granule exocytosis and downstream inflammation in a broad range of diseases. NKG7 expressed by CD4+ and CD8+ T cells played key roles in promoting inflammation during visceral leishmaniasis and malaria-two important parasitic diseases. Additionally, NKG7 expressed by natural killer cells was critical for controlling cancer initiation, growth and metastasis. NKG7 function in natural killer and CD8+ T cells was linked with their ability to regulate the translocation of CD107a to the cell surface and kill cellular targets, while NKG7 also had a major impact on CD4+ T cell activation following infection. Thus, we report a novel therapeutic target expressed on a range of immune cells with functions in different immune responses.

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