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

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

Andrabi, Syed Bilal Ahmad (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Buchacher, Tanja (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Khan, Mohd Moin (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Kalim, Ubaid Ullah (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Lindeman, Tuomas Mikael (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Alves, Marina Amaral (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Hinkkanen, Victoria (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Kemppainen, Esko (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Dickens, Alex M. (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; Department of Chemistry, University of Turku,Turku, Finland

Rasool, Omid (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Hyötyläinen, Tuulia, 1971- (author): Örebro universitet,Institutionen för naturvetenskap och teknik

Lahesmaa, Riitta (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Oresic, Matej, 1967- (author): Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

(creator_code:org_t)

Related links:: https://doi.org/10.1...; show more...; http://www.cell.com/...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

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)

By the author/editor: Sen, Partho, 198 ...; Andrabi, Syed Bi ...; Buchacher, Tanja; Khan, Mohd Moin; Kalim, Ubaid Ull ...; Lindeman, Tuomas ...; show more...; Alves, Marina Am ...; Hinkkanen, Victo ...; Kemppainen, Esko; Dickens, Alex M.; Rasool, Omid; Hyötyläinen, Tuu ...; Lahesmaa, Riitta; Oresic, Matej, 1 ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.