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Mesenchymal Stromal...
Mesenchymal Stromal Cells Disrupt mTOR-Signaling and Aerobic Glycolysis During T-Cell Activation
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Bottcher, M (författare)
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Hofmann, AD (författare)
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Bruns, H (författare)
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visa fler...
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Haibach, M (författare)
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Loschinski, R (författare)
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Saul, D (författare)
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Mackensen, A (författare)
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- Le Blanc, K (författare)
- Karolinska Institutet
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Jitschin, R (författare)
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Mougiakakos, D (författare)
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visa färre...
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(creator_code:org_t)
- 2015-11-17
- 2016
- Engelska.
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Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 34:2, s. 516-521
- Relaterad länk:
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https://stemcellsjou...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
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- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Bottcher, M
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Hofmann, AD
-
Bruns, H
-
Haibach, M
-
Loschinski, R
-
Saul, D
-
visa fler...
-
Mackensen, A
-
Le Blanc, K
-
Jitschin, R
-
Mougiakakos, D
-
visa färre...
- Artiklar i publikationen
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Stem cells (Dayt ...
- Av lärosätet
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Karolinska Institutet