Mesenchymal Stromal Cells Disrupt mTOR-Signaling and Aerobic Glycolysis During T-Cell Activation

Böttcher M, Hofmann AD, Bruns H, Haibach M, Loschinski R, Saul D, Mackensen A, Le Blanc K, Jitschin R, Mougiakakos D (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Stem Cells AlphaMed Press

Book Volume: 34

Pages Range: 516-21

Journal Issue: 2

DOI: 10.1002/stem.2234

Abstract

Mesenchymal stromal cells (MSCs) possess numerous regenerative and immune modulating functions. Transplantation across histocompatibility barriers is feasible due to their hypo-immunogenicity. MSCs have emerged as promising tools for treating graft-versus-host disease following allogeneic stem cell transplantation. It is well established that their clinical efficacy is substantially attributed to fine-tuning of T-cell responses. At the same time, increasing evidence suggests that metabolic processes control T-cell function and fate. Here, we investigated the MSCs' impact on the metabolic framework of activated T-cells. In fact, MSCs led to mitigated mTOR signaling. This phenomenon was accompanied by a weaker glycolytic response (including glucose uptake, glycolytic rate, and upregulation of glycolytic machinery) toward T-cell activating stimuli. Notably, MSCs express indoleamine-2,3-dioxygenase (IDO), which mediates T-cell suppressive tryptophan catabolism. Our observations suggest that IDO-induced tryptophan depletion interferes with a tryptophan-sufficiency signal that promotes cellular mTOR activation. Despite an immediate suppression of T-cell responses, MSCs foster a metabolically quiescent T-cell phenotype characterized by reduced mTOR signaling and glycolysis, increased autophagy, and lower oxidative stress levels. In fact, those features have previously been shown to promote generation of long-lived memory cells and it remains to be elucidated how MSC-induced metabolic effects shape in vivo T-cell immunity. Stem Cells 2016;34:516-521.

Authors with CRIS profile

Martin Böttcher Department of Medicine 5 – Haematology and Oncology Heiko Bruns Department of Medicine 5 – Haematology and Oncology Romy Böttcher-Loschinski Department of Medicine 5 – Haematology and Oncology Andreas Mackensen Lehrstuhl für Innere Medizin V Dimitrios Mougiakakos Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie

Involved external institutions

Karolinska University Hospital / Karolinska Universitetssjukhuset SE Sweden (SE)

How to cite

APA:

Böttcher, M., Hofmann, A.D., Bruns, H., Haibach, M., Loschinski, R., Saul, D.,... Mougiakakos, D. (2016). Mesenchymal Stromal Cells Disrupt mTOR-Signaling and Aerobic Glycolysis During T-Cell Activation. Stem Cells, 34(2), 516-21. https://dx.doi.org/10.1002/stem.2234

MLA:

Böttcher, Martin, et al. "Mesenchymal Stromal Cells Disrupt mTOR-Signaling and Aerobic Glycolysis During T-Cell Activation." Stem Cells 34.2 (2016): 516-21.

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