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

Nature immunology

Authors: 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, Marcela Montes de Oca, Siddharth Sankar Singh, Patrick T Bunn, Amy Roman Aguilera, Mika Casey, Matthias Braun, Nazanin Ghazanfari, Shivangi Wani, Yulin Wang, Fiona H Amante, Chelsea L Edwards, Ashraful Haque, William C Dougall, Om Prakash Singh, Alan G Baxter, Michele W L Teng, Alex Loukas, Norelle L Daly, Nicole Cloonan, Mariapia A Degli-Esposti, Jude Uzonna, William R Heath, Tobias Bald, Siok-Keen Tey, Kyohei Nakamura, Geoffrey R Hill, Rajiv Kumar, Shyam Sundar, Mark J Smyth, Christian R Engwerda

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.

PMID: 32839608

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