T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients
Glucocorticoids (GCs) are used to treat inflammatory disorders such as multiple sclerosis (MS) by exerting prominent activities in T cells including apoptosis induction and suppression of cytokine production. However, little is known about their impact on energy metabolism, although it is widely accepted that this process is a critical rheostat of T cell activity. We thus tested the hypothesis that GCs control genes and processes involved in nutrient transport and glycolysis. Our experiments revealed that escalating doses of dexamethasone (Dex) repressed energy metabolism in murine and human primary T cells. This effect was mediated by the GC receptor and unrelated to both apoptosis induction and Stat1 activity. In contrast, treatment of human T cells with rapamycin abolished the repression of metabolic gene expression by Dex, unveiling mTOR as a critical target of GC action. A similar phenomenon was observed in MS patients after intravenous methylprednisolon (IVMP) pulse therapy. The expression of metabolic genes was reduced in the peripheral blood T cells of most patients 24 h after GC treatment, an effect that correlated with disease activity. Collectively, our results establish the regulation of T cell energy metabolism by GCs as a new immunomodulatory principle.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Cells - 12(2023), 3 vom: 30. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Meyer-Heemsoth, Leonie [VerfasserIn] |
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| Links: |
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| Themen: |
7S5I7G3JQL |
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| Anmerkungen: |
Date Completed 14.02.2023 Date Revised 20.02.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/cells12030450 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM352765089 |
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| 100 | 1 | |a Meyer-Heemsoth, Leonie |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients |
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| 500 | |a Date Revised 20.02.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Glucocorticoids (GCs) are used to treat inflammatory disorders such as multiple sclerosis (MS) by exerting prominent activities in T cells including apoptosis induction and suppression of cytokine production. However, little is known about their impact on energy metabolism, although it is widely accepted that this process is a critical rheostat of T cell activity. We thus tested the hypothesis that GCs control genes and processes involved in nutrient transport and glycolysis. Our experiments revealed that escalating doses of dexamethasone (Dex) repressed energy metabolism in murine and human primary T cells. This effect was mediated by the GC receptor and unrelated to both apoptosis induction and Stat1 activity. In contrast, treatment of human T cells with rapamycin abolished the repression of metabolic gene expression by Dex, unveiling mTOR as a critical target of GC action. A similar phenomenon was observed in MS patients after intravenous methylprednisolon (IVMP) pulse therapy. The expression of metabolic genes was reduced in the peripheral blood T cells of most patients 24 h after GC treatment, an effect that correlated with disease activity. Collectively, our results establish the regulation of T cell energy metabolism by GCs as a new immunomodulatory principle | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a T cells | |
| 650 | 4 | |a glucocorticoids | |
| 650 | 4 | |a metabolism | |
| 650 | 4 | |a multiple sclerosis | |
| 650 | 7 | |a Glucocorticoids |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 700 | 1 | |a Mitschke, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Bier, Jasmina |e verfasserin |4 aut | |
| 700 | 1 | |a Schütz, Konstantin |e verfasserin |4 aut | |
| 700 | 1 | |a Villunger, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Legler, Tobias J |e verfasserin |4 aut | |
| 700 | 1 | |a Weber, Martin S |e verfasserin |4 aut | |
| 700 | 1 | |a Lühder, Fred |e verfasserin |4 aut | |
| 700 | 1 | |a Reichardt, Holger M |e verfasserin |4 aut | |
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