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High Metabolic Function and Resilience of NKG2A-Educated NK Cells

Natural killer (NK) cells are an important component of the innate immune system for the control of intracellular pathogens and cancer cells. NK cells demonstrate heterogeneous expression of inhibitory surface receptors. Signaling through these various receptors during NK cell development promotes f...

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Autores principales: Highton, Andrew J., Diercks, Björn-Philipp, Möckl, Franziska, Martrus, Gloria, Sauter, Jürgen, Schmidt, Alexander H., Bunders, Madeleine J., Körner, Christian, Guse, Andreas H., Altfeld, Marcus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554334/
https://www.ncbi.nlm.nih.gov/pubmed/33101277
http://dx.doi.org/10.3389/fimmu.2020.559576
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author Highton, Andrew J.
Diercks, Björn-Philipp
Möckl, Franziska
Martrus, Gloria
Sauter, Jürgen
Schmidt, Alexander H.
Bunders, Madeleine J.
Körner, Christian
Guse, Andreas H.
Altfeld, Marcus
author_facet Highton, Andrew J.
Diercks, Björn-Philipp
Möckl, Franziska
Martrus, Gloria
Sauter, Jürgen
Schmidt, Alexander H.
Bunders, Madeleine J.
Körner, Christian
Guse, Andreas H.
Altfeld, Marcus
author_sort Highton, Andrew J.
collection PubMed
description Natural killer (NK) cells are an important component of the innate immune system for the control of intracellular pathogens and cancer cells. NK cells demonstrate heterogeneous expression of inhibitory surface receptors. Signaling through these various receptors during NK cell development promotes functionality, referred to as NK cell education. Here we investigated the impact of education on NK cell metabolism through functional assessment of critical metabolic pathways and calcium signaling. Educated NK cells had an increased uptake of the metabolic substrates 2-NBDG, a fluorescent glucose analog, and BODIPY FL C(16), a fluorescent palmitate, compared to uneducated NK cells. Comparison of NK cells educated via KIRs or NKG2A showed that NKG2A-educated NK cells were the main contributor to these differences in uptake of metabolites, and that NKG2A-educated NK cells were functionally more resilient in response to metabolic blockade of oxidative phosphorylation. Furthermore, NKG2A-educated NK cells exhibited higher peak calcium concentration following stimulation, indicating stronger signaling events taking place in these educated NK cells. These results demonstrate that cellular metabolism plays an important role in the functional differences observed between educated and uneducated NK cells, and show that NKG2A-educated NK cells remain more functionally competent than KIR-educated NK cells when oxidative phosphorylation is restricted. Understanding metabolic programming during NK cell education may unveil future targets to manipulate NK cell function for use in clinical settings, such as cancer therapies.
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spelling pubmed-75543342020-10-22 High Metabolic Function and Resilience of NKG2A-Educated NK Cells Highton, Andrew J. Diercks, Björn-Philipp Möckl, Franziska Martrus, Gloria Sauter, Jürgen Schmidt, Alexander H. Bunders, Madeleine J. Körner, Christian Guse, Andreas H. Altfeld, Marcus Front Immunol Immunology Natural killer (NK) cells are an important component of the innate immune system for the control of intracellular pathogens and cancer cells. NK cells demonstrate heterogeneous expression of inhibitory surface receptors. Signaling through these various receptors during NK cell development promotes functionality, referred to as NK cell education. Here we investigated the impact of education on NK cell metabolism through functional assessment of critical metabolic pathways and calcium signaling. Educated NK cells had an increased uptake of the metabolic substrates 2-NBDG, a fluorescent glucose analog, and BODIPY FL C(16), a fluorescent palmitate, compared to uneducated NK cells. Comparison of NK cells educated via KIRs or NKG2A showed that NKG2A-educated NK cells were the main contributor to these differences in uptake of metabolites, and that NKG2A-educated NK cells were functionally more resilient in response to metabolic blockade of oxidative phosphorylation. Furthermore, NKG2A-educated NK cells exhibited higher peak calcium concentration following stimulation, indicating stronger signaling events taking place in these educated NK cells. These results demonstrate that cellular metabolism plays an important role in the functional differences observed between educated and uneducated NK cells, and show that NKG2A-educated NK cells remain more functionally competent than KIR-educated NK cells when oxidative phosphorylation is restricted. Understanding metabolic programming during NK cell education may unveil future targets to manipulate NK cell function for use in clinical settings, such as cancer therapies. Frontiers Media S.A. 2020-09-30 /pmc/articles/PMC7554334/ /pubmed/33101277 http://dx.doi.org/10.3389/fimmu.2020.559576 Text en Copyright © 2020 Highton, Diercks, Möckl, Martrus, Sauter, Schmidt, Bunders, Körner, Guse and Altfeld. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Highton, Andrew J.
Diercks, Björn-Philipp
Möckl, Franziska
Martrus, Gloria
Sauter, Jürgen
Schmidt, Alexander H.
Bunders, Madeleine J.
Körner, Christian
Guse, Andreas H.
Altfeld, Marcus
High Metabolic Function and Resilience of NKG2A-Educated NK Cells
title High Metabolic Function and Resilience of NKG2A-Educated NK Cells
title_full High Metabolic Function and Resilience of NKG2A-Educated NK Cells
title_fullStr High Metabolic Function and Resilience of NKG2A-Educated NK Cells
title_full_unstemmed High Metabolic Function and Resilience of NKG2A-Educated NK Cells
title_short High Metabolic Function and Resilience of NKG2A-Educated NK Cells
title_sort high metabolic function and resilience of nkg2a-educated nk cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554334/
https://www.ncbi.nlm.nih.gov/pubmed/33101277
http://dx.doi.org/10.3389/fimmu.2020.559576
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