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Quantitative genome...
Quantitative genome-scale metabolic modeling of human CD4+ T cell differentiation reveals subset-specific regulation of glycosphingolipid pathways
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- Sen, Partho, 1983- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Andrabi, Syed Bilal Ahmad (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Buchacher, Tanja (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Khan, Mohd Moin (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Kalim, Ubaid Ullah (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Lindeman, Tuomas Mikael (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Alves, Marina Amaral (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Hinkkanen, Victoria (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Kemppainen, Esko (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Dickens, Alex M. (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; Department of Chemistry, University of Turku,Turku, Finland
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- Rasool, Omid (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Hyötyläinen, Tuulia, 1971- (author)
- Örebro universitet,Institutionen för naturvetenskap och teknik
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- Lahesmaa, Riitta (author)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Oresic, Matej, 1967- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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(creator_code:org_t)
- Cell Press, 2021
- 2021
- English.
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In: Cell Reports. - : Cell Press. - 2211-1247. ; 37:6
- Related links:
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https://doi.org/10.1...
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http://www.cell.com/...
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https://urn.kb.se/re...
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Abstract
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- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- CD4(+) T cells
- ceramides
- gene expression
- genome-scale metabolic modeling
- glycosphingolipid metabolism
- lipid metabolism
- lipidomics
- metabolic pathways
- sphingolipids
- type 1 diabetes
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Sen, Partho, 198 ...
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Andrabi, Syed Bi ...
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Buchacher, Tanja
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Khan, Mohd Moin
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Kalim, Ubaid Ull ...
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Lindeman, Tuomas ...
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Alves, Marina Am ...
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Hinkkanen, Victo ...
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Kemppainen, Esko
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Dickens, Alex M.
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Rasool, Omid
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Hyötyläinen, Tuu ...
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Lahesmaa, Riitta
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Oresic, Matej, 1 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Cell Reports
- By the university
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Örebro University