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 Rinaldis,
Lisa G. M. Baarsen,
Claudia Kemper,
Peter Ghazal and
Andrew P. Cope ()
Additional contact information
Esperanza Perucha: King’s College London
Rossella Melchiotti: Guy’s and St Thomas’ NHS Foundation Trust and King’s College London
Jack A Bibby: King’s College London
Wing Wu: King’s College London
Klaus Stensgaard Frederiksen: Novo Nordisk A/S
Ceri A. Roberts: King’s College London
Zoe Hall: University of Cambridge
Gaelle LeFriec: King’s College London
Kevin A. Robertson: University of Edinburgh
Paul Lavender: King’s College London
Jens Gammeltoft Gerwien: Novo Nordisk A/S
Leonie S. Taams: King’s College London
Julian L. Griffin: University of Cambridge
Emanuele Rinaldis: Guy’s and St Thomas’ NHS Foundation Trust and King’s College London
Lisa G. M. Baarsen: University of Amsterdam
Claudia Kemper: King’s College London
Peter Ghazal: University of Edinburgh
Andrew P. Cope: King’s College London
Nature Communications, 2019, vol. 10, issue 1, 1-13
Abstract:
Abstract 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.
Date: 2019
References: Add references at CitEc
Citations:
Downloads: (external link)
https://www.nature.com/articles/s41467-019-08332-9 Abstract (text/html)
Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.
Export reference: BibTeX
RIS (EndNote, ProCite, RefMan)
HTML/Text
Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08332-9
Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/
DOI: 10.1038/s41467-019-08332-9
Access Statistics for this article
Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie
More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().