Hyperglycemic Memory of Innate Immune Cells Promotes In Vitro Proinflammatory Responses of Human Monocytes and Murine Macrophages
Copyright © 2021 by The American Association of Immunologists, Inc..
It has been well established that the presence of diabetes is accompanied by a chronic inflammatory state promoting various diabetes-associated complications. One potential driver of this enhanced inflammatory state in patients with diabetes is hyperglycemia. Even after blood glucose control is achieved, diabetes-associated complications persist, suggesting the presence of a "hyperglycemic memory." Innate immune cells, critically involved in various complications associated with diabetes, can build nonspecific, immunological memory (trained immunity) via epigenetic regulation. We examine the potential involvement of hyperglycemia-induced trained immunity in promoting inflammation. Our results show that hyperglycemia induces a trained phenotype in vivo in mice and in vitro in human monocytes, representative by an increased TNF-α secretion after ex vivo stimulation with LPS. These effects were largely mediated by epigenetic changes controlled by the mixed lineage leukemia (MLL) family because treatment with the MLL inhibitor menin-MLL during the process of trained immunity acquisition repressed the proinflammatory phenotype. Collectively, our results identify a novel link between hyperglycemia and inflammation in innate immune cells that might explain the increased proinflammatory state during diabetes potentially contributing to the development of various diabetes-associated complications.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:206 |
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| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 206(2021), 4 vom: 15. Feb., Seite 807-813 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Thiem, Kathrin [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Completed 19.07.2021 Date Revised 19.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4049/jimmunol.1901348 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM319950824 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 by The American Association of Immunologists, Inc. | ||
| 520 | |a It has been well established that the presence of diabetes is accompanied by a chronic inflammatory state promoting various diabetes-associated complications. One potential driver of this enhanced inflammatory state in patients with diabetes is hyperglycemia. Even after blood glucose control is achieved, diabetes-associated complications persist, suggesting the presence of a "hyperglycemic memory." Innate immune cells, critically involved in various complications associated with diabetes, can build nonspecific, immunological memory (trained immunity) via epigenetic regulation. We examine the potential involvement of hyperglycemia-induced trained immunity in promoting inflammation. Our results show that hyperglycemia induces a trained phenotype in vivo in mice and in vitro in human monocytes, representative by an increased TNF-α secretion after ex vivo stimulation with LPS. These effects were largely mediated by epigenetic changes controlled by the mixed lineage leukemia (MLL) family because treatment with the MLL inhibitor menin-MLL during the process of trained immunity acquisition repressed the proinflammatory phenotype. Collectively, our results identify a novel link between hyperglycemia and inflammation in innate immune cells that might explain the increased proinflammatory state during diabetes potentially contributing to the development of various diabetes-associated complications | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Keating, Samuel T |e verfasserin |4 aut | |
| 700 | 1 | |a Netea, Mihai G |e verfasserin |4 aut | |
| 700 | 1 | |a Riksen, Niels P |e verfasserin |4 aut | |
| 700 | 1 | |a Tack, Cees J |e verfasserin |4 aut | |
| 700 | 1 | |a van Diepen, Janna |e verfasserin |4 aut | |
| 700 | 1 | |a Stienstra, Rinke |e verfasserin |4 aut | |
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