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

Nat Commun. 2019 Jan 30;10(1):498. doi: 10.1038/s41467-019-08332-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atorvastatin / pharmacology
  • Cholesterol / biosynthesis*
  • Humans
  • Hydroxycholesterols / pharmacology
  • Interferon-gamma / metabolism*
  • Interleukin-10 / metabolism*
  • Th1 Cells / drug effects
  • Th1 Cells / metabolism*


  • Hydroxycholesterols
  • IL10 protein, human
  • Interleukin-10
  • 25-hydroxycholesterol
  • Interferon-gamma
  • Cholesterol
  • Atorvastatin