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Stéphanie Solier, Sebastian Müller, Tatiana Cañeque, Antoine Versini, Arnaud Mansart, Fabien Sindikubwabo, Leeroy Baron, Laila Emam, Pierre Gestraud, Gheorghe Dan Pantoş and 24 more
Inflammation is a complex physiological process triggered in response to harmful stimuli 1 . It involves cells of the immune system capable of clearing sources of injury and damaged tissues. Excessive inflammation can occur as a result of infection and is a hallmark of several diseases 2–4 . The molecular bases underlying inflammatory responses are not fully understood. Here we show that the cell surface glycoprotein CD44, which marks the acquisition of distinct cell phenotypes in the context of development, immunity and cancer progression, mediates the uptake of metals including copper. We identify a pool of chemically reactive copper (ii) in mitochondria of inflammatory macrophages that catalyses NAD(H) redox cycling by activating hydrogen peroxide. Maintenance of NAD + enables metabolic and epigenetic programming towards the inflammatory state. Targeting mitochondrial copper (ii) with supformin (LCC-12), a rationally designed dimer of metformin, induces a reduction of the NAD(H) pool, leading to metabolic and epigenetic states that oppose macrophage activation. LCC-12 interferes with cell plasticity in other settings and reduces inflammation in mouse models of bacterial and viral infections. Our work highlights the central role of copper as a regulator of cell plasticity and unveils a therapeutic strategy based on metabolic reprogramming and the control of epigenetic cell states.
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Solier, S., Müller, S., Cañeque, T., Versini, A., Mansart, A., Sindikubwabo, F., Baron, L., Emam, L., Gestraud, P., Pantoş, G. D., Gandon, V., Gaillet, C., Wu, T., Dingli, F., Loew, D., Baulande, S., Durand, S., Sencio, V., Robil, C., … Rodriguez, R. (2023). A druggable copper-signalling pathway that drives inflammation. Nature, 617(7960), 386–394. https://doi.org/10.1038/s41586-023-06017-4
Solier, Stéphanie, et al. "A druggable copper-signalling pathway that drives inflammation." Nature, vol. 617, no. 7960, 2023, pp. 386–394, https://doi.org/10.1038/s41586-023-06017-4.
Solier, Stéphanie, Sebastian Müller, Tatiana Cañeque, Antoine Versini, Arnaud Mansart, Fabien Sindikubwabo, Leeroy Baron, et al. "A druggable copper-signalling pathway that drives inflammation." Nature 617, no. 7960 (2023): 386–394. https://doi.org/10.1038/s41586-023-06017-4.
Solier S., Müller S., Cañeque T. [и др.] A druggable copper-signalling pathway that drives inflammation // Nature. — 2023. — Vol. 617, № 7960. — P. 386–394. — URL: https://doi.org/10.1038/s41586-023-06017-4
@article{solier2023druggable,
title = {{A druggable copper-signalling pathway that drives inflammation}},
author = {Stéphanie Solier and Sebastian Müller and Tatiana Cañeque and Antoine Versini and Arnaud Mansart and Fabien Sindikubwabo and Leeroy Baron and Laila Emam and Pierre Gestraud and Gheorghe Dan Pantoş and Vincent Gandon and Christine Gaillet and Ting‐Di Wu and Florent Dingli and Damarys Loew and Sylvain Baulande and Sylvère Durand and Valentin Sencio and Cyril Robil and François Trottein and David Péricat and Emmanuelle Näser and Céline Cougoule and Étienne Meunier and Anne-Laure Bègue and Hélène Salmon and Nicolas Manel and Alain Puisieux and Sarah Watson and Mark A. Dawson and Nicolas Servant and Guido Kroemer and Djillali Annane and Raphaël Rodriguez},
journal = {Nature},
year = {2023},
volume = {617},
number = {7960},
pages = {386--394},
doi = {10.1038/s41586-023-06017-4},
url = {https://doi.org/10.1038/s41586-023-06017-4}
}TY - JOUR AU - Solier, Stéphanie AU - Müller, Sebastian AU - Cañeque, Tatiana AU - Versini, Antoine AU - Mansart, Arnaud AU - Sindikubwabo, Fabien AU - Baron, Leeroy AU - Emam, Laila AU - Gestraud, Pierre AU - Pantoş, Gheorghe Dan AU - Gandon, Vincent AU - Gaillet, Christine AU - Wu, Ting‐Di AU - Dingli, Florent AU - Loew, Damarys AU - Baulande, Sylvain AU - Durand, Sylvère AU - Sencio, Valentin AU - Robil, Cyril AU - Trottein, François AU - Péricat, David AU - Näser, Emmanuelle AU - Cougoule, Céline AU - Meunier, Étienne AU - Bègue, Anne-Laure AU - Salmon, Hélène AU - Manel, Nicolas AU - Puisieux, Alain AU - Watson, Sarah AU - Dawson, Mark A. AU - Servant, Nicolas AU - Kroemer, Guido AU - Annane, Djillali AU - Rodriguez, Raphaël TI - A druggable copper-signalling pathway that drives inflammation JO - Nature VL - 617 IS - 7960 SP - 386 EP - 394 PY - 2023 DA - 2023/04/26 DO - 10.1038/s41586-023-06017-4 UR - https://doi.org/10.1038/s41586-023-06017-4 ER -
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