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.

• 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
• Journal: Nature immunology (Nat Immunol) Vol. 21 Issue 10 Pg. 1205-1218 (10 2020) ISSN: 1529-2916 [Electronic] United States
• PMID: 32839608 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Nkg7 protein, mouse

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Cytotoxicity, Immunologic
• Disease Models, Animal
• Exocytosis
• Humans
• Inflammation (immunology)
• Killer Cells, Natural (immunology)
• Leishmania donovani (physiology)
• Leishmaniasis, Visceral (immunology)
• Malaria (immunology)
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Plasmodium (physiology)
• Secretory Vesicles (metabolism)