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

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. NKG7 is a molecule well associated with NK cells but of unknown function. Engwerda and colleagues demonstrate that NKG7 is also associated with T(H)1 cells and is essential for type I and cytotoxic responses.