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

Ng, Susanna S., Rivera, Fabian De Labastida, Yan, Juming, Corvino, Dillon, Das, Indrajit, Zhang, Ping, Kuns, Rachel, Chauhan, Shashi Bhushan, Hou, Jiajie, Li, Xian-Yang, Frame, Teija C.M., McEnroe, Benjamin A., Moore, Eilish, Na, Jinrui, Engel, Jessica A., Soon, Megan S. F., Singh, Bhawana, Kueh, Andrew J., Herold, Marco J., de Oca, Marcela Montes, Singh, Siddharth Sankar, Bunn, Patrick T., Aguilera, Amy Roman, Casey, Mika, Braun, Matthias, Ghazanfari, Nazanin, Wani, Shivangi, Wang, Yulin, Amante, Fiona, Edwards, Chelsea L., Haque, Ashraful, Dougall, William C., Singh, Om Prakash, Baxter, Alan G., Teng, Michele W.L., Loukas, Alex, Daly, Norelle L., Cloonan, Nicole, Degli-esposti, Mariapia, Uzonna, Jude, Heath, William R., Bald, Tobias, Tey, Siok-Keen, Nakamura, Kyohei, Hill, Geoffrey R., Kumar, Rajiv, Sundar, Shyam, Smyth, Mark J, and Engwerda, Christian R. (2020) The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation. Nature Immunology, 21. pp. 1205-1217.

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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.

Item ID: 64368
Item Type: Article (Research - C1)
ISSN: 1529-2916
Keywords: Cancer, Immunopathogenesis, Infectious diseases, Inflammation
Copyright Information: Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Funders: National Health and Medical Research Council of Australia (NHMRC), National Institutes of Health Tropical Medicine Research Centre (TMRC), Griffith University (GU), Deutsche Krebshilfe, Indian government Department of Science and Technology, Banaras Hindu University, Indian Council of Medical Research
Projects and Grants: NHMRC grant 037304, NHMRC grant 1058685, NHMRC grant 1078671, NHMRC grant 1132519, NHMRC grant 1132975, NHMRC grant 1154265, TMRC grant (U19 AI074321), Deutsche Krebshilfe Dr. Mildred Scheel Stiftung für Krebsforschung scholarship, Indian Government INSPIRE Faculty grant (LSBM-109/IF-14), Indian Council of Medical Research Junior Research Fellowship
Date Deposited: 16 Sep 2020 07:38
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320499 Immunology not elsewhere classified @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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