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Perucha, Esperanza; Melchiotti, Rossella; Bibby, Jack A; Wu, Wing; Frederiksen, Klaus Stensgaard; Roberts, Ceri A.; Hall, Zoe; LeFriec, Gaelle; Robertson, Kevin A.; Lavender, Paul; Gerwien, Jens Gammeltoft; Taams, Leonie S.; Griffin, Julian L.; de Rinaldis, Emanuele; van Baarsen, Lisa G. M.; Kemper, Claudia; Ghazal, Peter; Cope, Andrew P.

The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells

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  • Medientyp: E-Artikel
  • Titel: The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells
  • Beteiligte: Perucha, Esperanza; Melchiotti, Rossella; Bibby, Jack A; Wu, Wing; Frederiksen, Klaus Stensgaard; Roberts, Ceri A.; Hall, Zoe; LeFriec, Gaelle; Robertson, Kevin A.; Lavender, Paul; Gerwien, Jens Gammeltoft; Taams, Leonie S.; Griffin, Julian L.; de Rinaldis, Emanuele; van Baarsen, Lisa G. M.; Kemper, Claudia; Ghazal, Peter; Cope, Andrew P.
  • Erschienen: Springer Science and Business Media LLC, 2019
  • Erschienen in: Nature Communications, 10 (2019) 1
  • Sprache: Englisch
  • DOI: 10.1038/s41467-019-08332-9
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: AbstractThe mechanisms controlling CD4+ T cell switching from an effector to an anti-inflammatory (IL-10+) phenotype play an important role in the persistence of chronic inflammatory diseases. Here, we identify the cholesterol biosynthesis pathway as a key regulator of this process. Pathway analysis of cultured cytokine-producing human T cells reveals a significant association between IL-10 and cholesterol metabolism gene expression. Inhibition of the cholesterol biosynthesis pathway with atorvastatin or 25-hydroxycholesterol during switching from IFNγ+ to IL-10+ shows a specific block in immune resolution, defined as a significant decrease in IL-10 expression. Mechanistically, the master transcriptional regulator of IL10 in T cells, c-Maf, is significantly decreased by physiological levels of 25-hydroxycholesterol. Strikingly, progression to rheumatoid arthritis is associated with altered expression of cholesterol biosynthesis genes in synovial biopsies of predisposed individuals. Our data reveal a link between sterol metabolism and the regulation of the anti-inflammatory response in human CD4+ T cells.
  • Zugangsstatus: Freier Zugang