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


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.

SUBMITTER: Ng SS 

PROVIDER: S-EPMC7965849 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Ng Susanna S SS   De Labastida Rivera Fabian F   Yan Juming J   Corvino Dillon D   Das Indrajit I   Zhang Ping P   Kuns Rachel R   Chauhan Shashi Bhushan SB   Hou Jiajie J   Li Xian-Yang XY   Frame Teija C M TCM   McEnroe Benjamin A BA   Moore Eilish E   Na Jinrui J   Engel Jessica A JA   Soon Megan S F MSF   Singh Bhawana B   Kueh Andrew J AJ   Herold Marco J MJ   Montes de Oca Marcela M   Singh Siddharth Sankar SS   Bunn Patrick T PT   Aguilera Amy Roman AR   Casey Mika M   Braun Matthias M   Ghazanfari Nazanin N   Wani Shivangi S   Wang Yulin Y   Amante Fiona H FH   Edwards Chelsea L CL   Haque Ashraful A   Dougall William C WC   Singh Om Prakash OP   Baxter Alan G AG   Teng Michele W L MWL   Loukas Alex A   Daly Norelle L NL   Cloonan Nicole N   Degli-Esposti Mariapia A MA   Uzonna Jude J   Heath William R WR   Bald Tobias T   Tey Siok-Keen SK   Nakamura Kyohei K   Hill Geoffrey R GR   Kumar Rajiv R   Sundar Shyam S   Smyth Mark J MJ   Engwerda Christian R CR  

Nature immunology 20200824 10


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<sup>+</sup> and CD8<sup>+</sup> T cells played key roles in promoting inflammation during visceral leishmanias  ...[more]

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