The integration of metabolic and proteomic data uncovers an augmentation of the sphingolipid biosynthesis pathway during T-cell differentiation.

Autor: Kanno T; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Konno R; Department of Applied Genomics Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Sato M; Department of Research and Development, Kazusa DNA Research Institutes, Kisarazu, Japan., Kurabayashi A; Department of Research and Development, Kazusa DNA Research Institutes, Kisarazu, Japan., Miyako K; Department of Applied Genomics Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Nakajima T; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Yokoyama S; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Sasamoto S; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Asou HK; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Ohzeki J; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Hasegawa Y; Department of Applied Genomics Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Ikeda K; Department of Applied Genomics Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Kawashima Y; Department of Applied Genomics Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Ohara O; Department of Applied Genomics Kazusa DNA Research Institute, Kisarazu, Chiba, Japan., Endo Y; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan. endo@kazusa.or.jp.; Department of Omics Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan. endo@kazusa.or.jp.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 May 23; Vol. 7 (1), pp. 622. Date of Electronic Publication: 2024 May 23.
DOI: 10.1038/s42003-024-06339-7
Abstrakt: Recent studies have highlighted the significance of cellular metabolism in the initiation of clonal expansion and effector differentiation of T cells. Upon exposure to antigens, naïve CD4 + T cells undergo metabolic reprogramming to meet their metabolic requirements. However, only few studies have simultaneously evaluated the changes in protein and metabolite levels during T cell differentiation. Our research seeks to fill the gap by conducting a comprehensive analysis of changes in levels of metabolites, including sugars, amino acids, intermediates of the TCA cycle, fatty acids, and lipids. By integrating metabolomics and proteomics data, we discovered that the quantity and composition of cellular lipids underwent significant changes in different effector Th cell subsets. Especially, we found that the sphingolipid biosynthesis pathway was commonly activated in Th1, Th2, Th17, and iTreg cells and that inhibition of this pathway led to the suppression of Th17 and iTreg cells differentiation. Additionally, we discovered that Th17 and iTreg cells enhance glycosphingolipid metabolism, and inhibition of this pathway also results in the suppression of Th17 and iTreg cell generation. These findings demonstrate that the utility of our combined metabolomics and proteomics analysis in furthering the understanding of metabolic transition during Th cell differentiation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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