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Mesenchymal Stromal...
Mesenchymal Stromal Cells Disrupt mTOR-Signaling and Aerobic Glycolysis During T-Cell Activation
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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2015-11-17
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Oxford University Press (OUP),2016
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:133023801
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http://kipublications.ki.se/Default.aspx?queryparsed=id:133023801URI
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https://doi.org/10.1002/stem.2234DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Added entries (persons, corporate bodies, meetings, titles ...)
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Hofmann, AD
(author)
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Bruns, H
(author)
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Haibach, M
(author)
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Loschinski, R
(author)
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Saul, D
(author)
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Mackensen, A
(author)
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Le Blanc, KKarolinska Institutet
(author)
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Jitschin, R
(author)
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Mougiakakos, D
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:Stem cells (Dayton, Ohio): Oxford University Press (OUP)34:2, s. 516-5211549-49181066-5099
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- By the author/editor
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Bottcher, M
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Hofmann, AD
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Bruns, H
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Haibach, M
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Loschinski, R
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Saul, D
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show more...
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Mackensen, A
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Le Blanc, K
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Jitschin, R
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Mougiakakos, D
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Stem cells (Dayt ...
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Karolinska Institutet