Journal article

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

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 CM Frame, Benjamin A McEnroe, Eilish Moore, Jinrui Na, Jessica A Engel, Megan SF Soon, Bhawana Singh, Andrew J Kueh, Marco J Herold, Marcela Montes de Oca Show all

NATURE IMMUNOLOGY | NATURE PUBLISHING GROUP | Published : 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+ 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 ..

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by National Institutes of Health Tropical Medicine Research Centre (TMRC) grant


Awarded by INSPIRE Faculty grant by the Indian government Department of Science and Technology (DST), Banaras Hindu University


Awarded by University Grants Commission


Funding Acknowledgements

We thank the staff at the Kala-Azar Medical Research Centre (KAMRC), Muzaffarpur, India for help with the collection of blood samples, as well as patients and volunteers for allowing the use of blood samples. We thank staff at the QIMR Berghofer flow cytometry laboratory for assistance, and staff at the QIMR Berghofer animal facility for animal husbandry. We acknowledge the facilities, and the scientific and technical assistance of the MAGEC, Walter and Eliza Hall Institute of Medical Research. The MAGEC is supported by the Australian Phenomics Network (APN) and the APN is supported by the Australian government through the National Collaborative Research Infrastructure Strategy program. We thank the NIH tetramer facility (Atlanta, GA, United States) for production of the I-Ab-PEPCK335-351 tetramer used to detect L. donovani PEPCK-specific CD4+ T cells in these studies. This work was made possible through Queensland State Government funding and grants and fellowships from the National Health and Medical Research Council of Australia (NHMRC; grant numbers 1037304, 1058685, 1078671, 1132519, 1132975 and 1154265). Funding was also provided through a National Institutes of Health Tropical Medicine Research Centre (TMRC) grant (U19 AI074321), as well as Australian post-graduate awards through Griffith University's Institute of Glycomics and School of Natural Sciences to P.T.B. and S.S.N., respectively; a Dr. Mildred Scheel Stiftung fur Krebsforschung scholarship from Deutsche Krebshilfe to M.B.; and an INSPIRE Faculty grant (LSBM-109/IF-14) provided by the Indian government Department of Science and Technology (DST), Banaras Hindu University and University Grants Commission (M-14-70) to R.K. B.S. was supported by a Junior Research Fellowship from the Indian Council of Medical Research.