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

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

*Corresponding author for this work
3 Citations (Scopus)


The 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.

Original languageEnglish
Article number498
JournalNature Communications
Issue number1
Pages (from-to)498
Publication statusPublished - 30.01.2019

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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