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The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation.
- Source :
-
Nature immunology [Nat Immunol] 2020 Oct; Vol. 21 (10), pp. 1205-1218. Date of Electronic Publication: 2020 Aug 24. - Publication Year :
- 2020
-
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 <superscript>+</superscript> and CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> 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.
- Subjects :
- Animals
Cells, Cultured
Cytotoxicity, Immunologic
Disease Models, Animal
Exocytosis
Humans
Membrane Proteins genetics
Mice
Mice, Inbred C57BL
Secretory Vesicles metabolism
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Inflammation immunology
Killer Cells, Natural immunology
Leishmania donovani physiology
Leishmaniasis, Visceral immunology
Malaria immunology
Membrane Proteins metabolism
Plasmodium physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 21
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32839608
- Full Text :
- https://doi.org/10.1038/s41590-020-0758-6