Abstract
Cholesterol is a member of the sterol family that plays essential roles in biological processes, including cell membrane stability and myelin formation. Cholesterol can be metabolized into several molecules including bile acids, hormones, and oxysterols. Studies from the last few decades have demonstrated that oxysterols are not only active metabolites but are further involved in the modulation of immune responses. Liver X Receptors (LXRs), nuclear receptors for oxysterols, are important for cholesterol homeostasis and regulation of inflammatory response but are still poorly characterized during autoimmune diseases. Here we review the current knowledge about the role of oxysterols during autoimmune conditions and focus on the implication of LXR-dependent and LXR-independent pathways. We further highlight the importance of these pathways in particular during central nervous system (CNS) autoimmunity and inflammatory bowel diseases (IBD) in both experimental models and human studies. Finally, we discuss our vision about future applications and research on oxysterols related to autoimmunity.
Highlights
Cholesterol is implicated in several biochemistry processes of the body
We further highlight the importance of these pathways in particular during central nervous system (CNS) autoimmunity and inflammatory bowel diseases (IBD) in both experimental models and human studies
Even if the precise role of Liver X Receptors (LXRs) pathway in CNS autoimmunity remains to be further investigated, modulation of the LXR pathway and their target genes are involved in a metabolic checkpoint during Th17 cell differentiation which is important in Multiple sclerosis (MS) and EAE diseases [71]
Summary
Cholesterol is implicated in several biochemistry processes of the body It is an essential component of the mammalian cells accounting for up to 25% of all membrane lipids [1]. Cholesterol can interact with integral membrane proteins and modulate their functions [1]. It is a precursor of important molecules such as vitamin D, bile acids, steroid hormones, and oxysterols. Oxysterols are downstream metabolites of cholesterol oxidation They can be divided into two categories called primary and secondary oxysterols. In addition to the modulation of cholesterol levels, oxysterols are precursors of bile acid production and steroid hormones acting as intermediates in their synthesis.
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