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  • While oxysterols were most extensively studied

    2020-11-20

    While oxysterols were most extensively studied for its potent ability to mediate feedback regulation of cholesterol biosynthesis, some early investigations showed that the enzymes involved in its syntheses were highly upregulated in macrophages and dendritic cells—an indication of possible roles in immune related functions., Subsequent research has shown that oxysterols have a broad range of roles in innate and adaptive immune responses. For example, 25-hydroxycholesterol (25-HC) is induced in macrophages by type 1 interferon (IFN) signaling and has broad ability to prevent viral entry, replication and budding., In addition to the pro-inflammatory effects, many studies show that, 25-HC also mediate the anti-inflammatory effects downstream of the IFN pathway. Immunomodulation effects of certain oxysterols were previously shown to depend on activation of oxysterol-binding liver X receptors (LXRs). Recent work from our labs as well as from others has shown additional receptors linking oxysterols and immunity. For example, we found that 7α,25-dihydroxycholesterol as a key molecule involved in directing the migration of naive B cells, T L-Kynurenine mg and dendritic cells by engaging an orphan GPCR, GPR183, a gene which was initially found to be highly induced by Epstein–Barr virus infection of B cells. In another study, an oxysterol was found to be the most potent endogenous ligand of RORγt, an orphan nuclear receptor whose activation is the key step in the downstream production of IL-17—a key inflammatory pathway in several autoimmune disorders. Thus, many new biological functions of oxysterols, especially their broad range of roles as signaling molecules in the innate and adaptive immune system continues to be discovered and hold the promise of finding new targets for the therapeutic intervention for autoimmune disorders such as psoriasis, RA, IBD, and MS.,
    It is now widely accepted that oxysterols are more than metabolic intermediates but are actually lipid mediators. To qualify as a lipid mediator, a lipid compound should meet three conditions. First to be endogenous, second to have its levels altered depending on the physiological or pathological situation, and third to induce a signaling response when its levels are altered. As is evident from the papers published in this , oxysterols largely qualify as lipid mediators. First, they are endogenously produced, for the most part from cholesterol, via enzymatic reactions or following oxidation by reactive oxygen species. Second, the number of situations where altered oxysterol levels have been reported is continuing to increase. Such alterations have been described in situations as diverse as diseases of the cardiovascular system, central nervous system, eyes, the metabolic syndrome or cancer. Third, oxysterols can induce signaling responses either by altering cell membrane properties or by binding and activating several receptors. Any web-based literature search shows how the field is rapidly expanding. This is, not in small part, due to the “ENOR initiative” launched by Dr Iuliano and Dr Lizard in 2010 (). The European Network for Oxysterol Research (ENOR), via regular meetings and symposia, has helped moving the field forward by facilitating discussions and collaborations. In September 2017, we held in Brussels the seventh ENOR symposium entitled “Oxysterols and sterol derivatives in health and disease”. As for the previous meetings, this seventh edition was rich in high-level talks and intense scientific discussions. This special issue of “Biochimie” entitled “” is intended to convey these interesting research topics to a larger community, via both original reviews and research papers.
    Introduction ILCs are recombination activating gene (RAG)-independent lymphocytes that originate from a common lymphoid progenitor and are present throughout the body with higher frequencies at mucosal surfaces (Figure 1). ILCs have emerged as critical regulators of mucosal barrier integrity, particularly in the intestine, lungs and skin where they reside and respond rapidly to environmental stimuli and impact subsequent adaptive immune responses [1, 2, 3]. Moreover, ILCs have been shown to contribute to viral immunosurveillance of the liver [4] and homeostasis of adipose tissue [5, 6, 7]. Thus, their functions range from host defense to metabolic homeostasis.