Interleukin-27 drives oxysterol production that regulate the adaptive Immune response

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