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  • Bottcher, M (author)

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

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2015-11-17
  • Oxford University Press (OUP),2016

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:133023801
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:133023801URI
  • https://doi.org/10.1002/stem.2234DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 ...)

  • Hofmann, AD (author)
  • Bruns, H (author)
  • Haibach, M (author)
  • Loschinski, R (author)
  • Saul, D (author)
  • Mackensen, A (author)
  • Le Blanc, KKarolinska Institutet (author)
  • Jitschin, R (author)
  • Mougiakakos, D (author)
  • Karolinska Institutet (creator_code:org_t)

Related titles

  • In:Stem cells (Dayton, Ohio): Oxford University Press (OUP)34:2, s. 516-5211549-49181066-5099

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