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  • Sen, Partho,1983-Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)

Quantitative genome-scale metabolic modeling of human CD4+ T cell differentiation reveals subset-specific regulation of glycosphingolipid pathways

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • Cell Press,2021
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-95400
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-95400URI
  • https://doi.org/10.1016/j.celrep.2021.109973DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Funding agencies:Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research (SyMMyS) 250114Sigrid Juselius FoundationJane and Aatos Erkko FoundationFinnish Cancer FoundationJuvenile Diabetes Research Foundation 2-SRA-2014-159-Q-R
  • T cell activation, proliferation, and differentiation involve metabolic reprogramming resulting from the interplay of genes, proteins, and metabolites. Here, we aim to understand the metabolic pathways involved in the activation and functional differentiation of human CD4+ T cell subsets (T helper [Th]1, Th2, Th17, and induced regulatory T [iTreg] cells). Here, we combine genome-scale metabolic modeling, gene expression data, and targeted and non-targeted lipidomics experiments, together with in vitro gene knockdown experiments, and show that human CD4+ T cells undergo specific metabolic changes during activation and functional differentiation. In addition, we confirm the importance of ceramide and glycosphingolipid biosynthesis pathways in Th17 differentiation and effector functions. Through in vitro gene knockdown experiments, we substantiate the requirement of serine palmitoyltransferase (SPT), a de novo sphingolipid pathway in the expression of proinflammatory cytokines (interleukin [IL]-17A and IL17F) by Th17 cells. Our findings provide a comprehensive resource for selective manipulation of CD4+ T cells under disease conditions characterized by an imbalance of Th17/natural Treg (nTreg) cells.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Andrabi, Syed Bilal AhmadTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Buchacher, TanjaTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Khan, Mohd MoinTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Kalim, Ubaid UllahTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Lindeman, Tuomas MikaelTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Alves, Marina AmaralTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Hinkkanen, VictoriaTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Kemppainen, EskoTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Dickens, Alex M.Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; Department of Chemistry, University of Turku,Turku, Finland (author)
  • Rasool, OmidTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Hyötyläinen, Tuulia,1971-Örebro universitet,Institutionen för naturvetenskap och teknik(Swepub:oru)tihn (author)
  • Lahesmaa, RiittaTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland(Swepub:oru)moc (author)
  • Örebro universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

Related titles

  • In:Cell Reports: Cell Press37:62211-1247

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