The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30700717.
- Also identified by DOI 10.1038/s41467-019-08332-9 and PMC identifier 6353904.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The mechanisms controlling CD4<sup>+</sup> T cell switching from an effector to an anti-inflammatory (IL-10<sup>+</sup>) 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<sup>+</sup> to IL-10<sup>+</sup> 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<sup>+</sup> T cells.
Medical subject headings
- Cholesterol
- Interferon-gamma
- Interleukin-10
- Th1 Cells