Acid ceramidase regulates innate immune memory
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
Innate immune memory, also called "trained immunity," is a functional state of myeloid cells enabling enhanced immune responses. This phenomenon is important for host defense, but also plays a role in various immune-mediated conditions. We show that exogenously administered sphingolipids and inhibition of sphingolipid metabolizing enzymes modulate trained immunity. In particular, we reveal that acid ceramidase, an enzyme that converts ceramide to sphingosine, is a potent regulator of trained immunity. We show that acid ceramidase regulates the transcription of histone-modifying enzymes, resulting in profound changes in histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation. We confirm our findings by identifying single-nucleotide polymorphisms in the region of ASAH1, the gene encoding acid ceramidase, that are associated with the trained immunity cytokine response. Our findings reveal an immunomodulatory effect of sphingolipids and identify acid ceramidase as a relevant therapeutic target to modulate trained immunity responses in innate immune-driven disorders.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 12 vom: 26. Dez., Seite 113458 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rother, Nils [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.01.2024 Date Revised 01.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.113458 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Innate immune memory, also called "trained immunity," is a functional state of myeloid cells enabling enhanced immune responses. This phenomenon is important for host defense, but also plays a role in various immune-mediated conditions. We show that exogenously administered sphingolipids and inhibition of sphingolipid metabolizing enzymes modulate trained immunity. In particular, we reveal that acid ceramidase, an enzyme that converts ceramide to sphingosine, is a potent regulator of trained immunity. We show that acid ceramidase regulates the transcription of histone-modifying enzymes, resulting in profound changes in histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation. We confirm our findings by identifying single-nucleotide polymorphisms in the region of ASAH1, the gene encoding acid ceramidase, that are associated with the trained immunity cytokine response. Our findings reveal an immunomodulatory effect of sphingolipids and identify acid ceramidase as a relevant therapeutic target to modulate trained immunity responses in innate immune-driven disorders | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a acid ceramidase | |
| 650 | 4 | |a epigenetics | |
| 650 | 4 | |a immune memory | |
| 650 | 4 | |a innate immunity | |
| 650 | 4 | |a lipid metabolism | |
| 650 | 4 | |a monocytes | |
| 650 | 4 | |a nanobiologics | |
| 650 | 4 | |a sphingolipids | |
| 650 | 4 | |a trained immunity | |
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| 700 | 1 | |a Yanginlar, Cansu |e verfasserin |4 aut | |
| 700 | 1 | |a Prévot, Geoffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Jonkman, Inge |e verfasserin |4 aut | |
| 700 | 1 | |a Jacobs, Maaike |e verfasserin |4 aut | |
| 700 | 1 | |a van Leent, Mandy M T |e verfasserin |4 aut | |
| 700 | 1 | |a van Heck, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Matzaraki, Vasiliki |e verfasserin |4 aut | |
| 700 | 1 | |a Azzun, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Morla-Folch, Judit |e verfasserin |4 aut | |
| 700 | 1 | |a Ranzenigo, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, William |e verfasserin |4 aut | |
| 700 | 1 | |a van der Meel, Roy |e verfasserin |4 aut | |
| 700 | 1 | |a Fayad, Zahi A |e verfasserin |4 aut | |
| 700 | 1 | |a Riksen, Niels P |e verfasserin |4 aut | |
| 700 | 1 | |a Hilbrands, Luuk B |e verfasserin |4 aut | |
| 700 | 1 | |a Lindeboom, Rik G H |e verfasserin |4 aut | |
| 700 | 1 | |a Martens, Joost H A |e verfasserin |4 aut | |
| 700 | 1 | |a Vermeulen, Michiel |e verfasserin |4 aut | |
| 700 | 1 | |a Joosten, Leo A B |e verfasserin |4 aut | |
| 700 | 1 | |a Netea, Mihai G |e verfasserin |4 aut | |
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| 700 | 1 | |a Teunissen, Abraham J P |e verfasserin |4 aut | |
| 700 | 1 | |a Duivenvoorden, Raphaël |e verfasserin |4 aut | |
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