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bioRxiv · 10.1101/2020.01.31.928200

LAG3 is a Central Regulator of NK Cell Cytokine Production

Narayanan, S.·Ahl, P. J.·Au, V. B.·Kaliaperumal, N.·Lim, S. G.·Wang, C.-I.·Fairhurst, A.-M.·Connolly, J. E.
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Abstract

Natural killer (NK) cells are innate effectors, which play a crucial role in controlling viral infections. Administration of IFN- has shown promising results as a therapeutic, controlling HIV, and chronic viral hepatitis. However the downstream mechanisms by which IFN- mediates its anti-viral effects is largely unknown. In this investigation, we evaluated the impact of IFN- on peripheral blood NK cells from healthy donors. High dimensional flow cytometry analysis of NK cell surface receptors following exposure to IFN- showed an increased expression of the check point inhibitor LAG3. Further characterization revealed that LAG3 was expressed in a subset of NK cells with high expression of activation and maturation markers. Assessment of metabolic pathways showed that LAG3+ NK cells had enhanced rates of glycolysis and glycolytic capacity, suggesting that it is a primed effector subset with enhanced glucose metabolism. Inhibition of LAG3 on NK cells using antibody in vitro resulted in a profound increase in secretion of cytokines IFN-{gamma}, TNF-, MIP-1 and MIP-1{beta}, without affecting the cytotoxic activity. Taken together, these results showed that LAG3 is a negative regulator of cytokine production by mature NK cells.

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Narayanan, S., Ahl, P. J., Au, V. B., Kaliaperumal, N., Lim, S. G., Wang, C.-I., Fairhurst, A.-M., Connolly, J. E.. 2020-02-02. LAG3 is a Central Regulator of NK Cell Cytokine Production. https://doi.org/10.1101/2020.01.31.928200

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