T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients

Meyer-Heemsoth, Leonie; Mitschke, Katja; Bier, Jasmina; Schütz, Konstantin; Villunger, Andreas; Legler, Tobias J.; Weber, Martin S.; Lühder, Fred; Reichardt, Holger M.

doi:10.3390/cells12030450

Open AccessArticle

T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients

by

Leonie Meyer-Heemsoth

^1,†,

Katja Mitschke

^1,†,

Jasmina Bier

^2,†

,

Konstantin Schütz

³,

Andreas Villunger

⁴

,

Tobias J. Legler

⁵

,

Martin S. Weber

^3,6,7,

Fred Lühder

^2,†

and

Holger M. Reichardt

^1,*,†

¹

Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, 37073 Göttingen, Germany

²

Institute for Neuroimmunology and Multiple Sclerosis Research, University Medical Center Göttingen, 37075 Göttingen, Germany

³

Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany

⁴

Institute of Developmental Immunology, Medical University of Innsbruck, 6020 Innsbruck, Austria

⁵

Department of Transfusion Medicine, University Medical Center Göttingen, 37075 Göttingen, Germany

⁶

Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany

⁷

Fraunhofer-Institute for Translational Medicine and Pharmacology ITMP, 37075 Göttingen, Germany

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cells 2023, 12(3), 450; https://doi.org/10.3390/cells12030450

Submission received: 27 December 2022 / Revised: 24 January 2023 / Accepted: 29 January 2023 / Published: 30 January 2023

(This article belongs to the Special Issue Study around Neuroinflammation—Series 3)

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Abstract

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.

Keywords: glucocorticoids; T cells; multiple sclerosis; metabolism

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MDPI and ACS Style

Meyer-Heemsoth, L.; Mitschke, K.; Bier, J.; Schütz, K.; Villunger, A.; Legler, T.J.; Weber, M.S.; Lühder, F.; Reichardt, H.M. T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients. Cells 2023, 12, 450. https://doi.org/10.3390/cells12030450

AMA Style

Meyer-Heemsoth L, Mitschke K, Bier J, Schütz K, Villunger A, Legler TJ, Weber MS, Lühder F, Reichardt HM. T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients. Cells. 2023; 12(3):450. https://doi.org/10.3390/cells12030450

Chicago/Turabian Style

Meyer-Heemsoth, Leonie, Katja Mitschke, Jasmina Bier, Konstantin Schütz, Andreas Villunger, Tobias J. Legler, Martin S. Weber, Fred Lühder, and Holger M. Reichardt. 2023. "T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients" Cells 12, no. 3: 450. https://doi.org/10.3390/cells12030450

APA Style

Meyer-Heemsoth, L., Mitschke, K., Bier, J., Schütz, K., Villunger, A., Legler, T. J., Weber, M. S., Lühder, F., & Reichardt, H. M. (2023). T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients. Cells, 12(3), 450. https://doi.org/10.3390/cells12030450

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T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients

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