Vigne, Solenne , Fanny, Chalmin, Duc, Donovan , Clottu, Aurélie , Apetoh, Lionel, Marc, Lobaccaro, Pot, Caroline , Zhang, Juan and Christen, Isabelle (2017) Interleukin-27 drives oxysterol production that regulate the adaptive Immune response. Frontiers in immunology, 8. ISSN 1664-3224

Abstract

Oxysterols, oxidized forms of cholesterol, have pleiotropic roles on the immune response aside from their involvement in lipid metabolism. The oxysterols 25-hydroxycholesterol (25-OHC) and 725-dihydroxycholesterol (725-OHC) regulate antiviral immunity and immune cell chemotaxis. However their physiological effects on adaptive immune response in particular on CD4+ T lymphocytes are largely unknown. Here we assessed oxysterol levels in subset of CD4+ T cells and demonstrated that 25-OHC and transcript levels of its synthesizing enzyme, cholesterol 25 hydroxylase (Ch25h), were specifically increased in IL-27-induced Type 1 regulatory T (TR1) cells. We further showed that 25-OHC acts as negative regulator of TR1 cells in particular of IL-10 secretion via LXR signaling. Not only do these findings unravel novel molecular mechanisms accounting for IL-27 signaling but they also highlight lipids as critical modulators of adaptive immunity.

Item Type:	Article
Date Deposited:	07 Nov 2017 00:45
Last Modified:	07 Nov 2017 00:45
URI:	https://oak.novartis.com/id/eprint/33385