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

Ng, Susanna S; De Labastida Rivera, Fabian; 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; Montes de Oca, Marcela; Singh, Siddharth Sankar; Bunn, Patrick T; Aguilera, Amy Roman; Casey, Mika; Braun, Matthias; Ghazanfari, Nazanin; Wani, Shivangi; Wang, Yulin; Amante, Fiona H; 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 A; Uzonna, Jude; Heath, William R; Bald, Tobias; Tey, Siok-Keen; Nakamura, Kyohei; Hill, Geoffrey R; Kumar, Rajiv; Sundar, Shyam; Smyth, Mark J; Engwerda, Christian R

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.