Quantitative analysis of human CD4+T-cell differentiation reveals subset-specific regulation of glycosphingolipid pathways

Sen, Partho (author): 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; InFLAMES Research Flagship Center, University of Turku, Turku, Finland

Buchacher, Tanja (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland

Khan, Mohd Moin (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland

Ullah, Ubaid (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 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

Rasool, Omid (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland

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

Lahesmaa, Riitta (author): Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 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)

John Wiley & Sons, 2021
2021
English.
In: European Journal of Immunology. - : John Wiley & Sons. - 0014-2980 .- 1521-4141. ; 51:Suppl. 1, s. 237-237

Abstract Subject headings

T‐cells are sentinels of adaptive immune responses. T‐cell activation, proliferation and differentiation involves metabolic reprogramming involving 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 (Th1, Th2, Th17 and iTregs). We combined genome‐scale metabolic modeling, gene expression data, targeted and non‐targeted lipidomics experiments, together with in vitro gene knockdown experiments and showed that human CD4+ T cells undergo specific metabolic changes during activation and functional differentiation. In addition, we identified and confirmed the importance of ceramide and glycosphingolipid biosynthesis pathways in Th17 differentiation and effector functions. Through in vitro gene knockdown experiments, we substantiated the requirement of serine palmitoyl transferase, a de novo sphingolipid pathway in the expression of proinflammatory cytokine (IL17A and IL17F) by Th17 cells. Our findings may provide a comprehensive resource for identifying CD4+ T‐cell‐specific targets for their selective manipulation under disease conditions, particularly, diseases characterized by an imbalance of Th17/nTreg cells.

By the author/editor: Sen, Partho; Andrabi, Syed Bi ...; Buchacher, Tanja; Khan, Mohd Moin; Ullah, Ubaid; 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 ...

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