Diverse Immunoregulatory Roles of Oxysterols—The Oxidized Cholesterol Metabolites

Abstract

Intermediates of both cholesterol synthesis and cholesterol metabolism can have diverse roles in the control of cellular processes that go beyond the control of cholesterol homeostasis. For example, oxidized forms of cholesterol, called oxysterols have functions ranging from the control of gene expression, signal transduction and cell migration. This is of particular interest in the context of immunology and immunometabolism where we now know that metabolic processes are key towards shaping the nature of immune responses. Equally, aberrant metabolic processes including altered cholesterol homeostasis contribute to immune dysregulation and dysfunction in pathological situations. This review article brings together our current understanding of how oxysterols affect the control of immune responses in diverse immunological settings.

7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19

“…Among the oxysterols with strong anti-viral properties are mainly those derived from cholesterol oxidation on the aliphatic side chain such as 25-hydroxycholesterol and 27-hydroxycholesterol, which could act both by inhibiting viral replication and by activating the immune response [ 63 , 46 , 64 , 65 ]. 7α, 25-hydroxycholesterol generated by cholesterol by the sequential action of cholesterol 25 hydroxylase (CH25 H) and 7-alpha-hydroxylase (CYP7B1) also has anti-viral activities, and acts as chemo-attractant for cells expressing the cell surface receptor GPR183 present on dendritic and B cells, as well as type 3 innate lymphoid cells (ILC3) [ 66 , 67 ]. Less potent antiviral activities have been reported with 7β-hydroxycholesterol and 7KC [ 61 ].…”

Cholesterol Hydroxylating Cytochrome P450 46A1: From Mechanisms of Action to Clinical Applications

“…Finally, a list of pressing questions will be offered from the viewpoints of a biochemist (IAP), who pioneered the investigation of CYP46A1 pharmacological modulations and is now identifying brain processes affected by CYP46A1 activity, and a gene therapy neuroscientist (NC), aiming to ultimately bring this therapeutic target to patients affected with severe neurodegenerative diseases. More comprehensive reviews on CYP46A1, oxysterols, and the links between CYP46A1, cholesterol homeostasis in the brain, and neurological disorders can be found elsewhere ( Russell et al, 2009 ; Moutinho et al, 2016 ; Bjorkhem et al, 2019 ; Loera-Valencia et al, 2019 ; Petrov and Pikuleva, 2019 ; Choi and Finlay, 2020 ; Griffiths and Wang, 2020 ; Sodero, 2020 ).…”

Intestinal Transcriptome Analysis Reveals Enrichment of Genes Associated with Immune and Lipid Mechanisms, Favoring Soybean Meal Tolerance in High-Growth Zebrafish (Danio Rerio)

“…Along with MUFAs and PUFAs, cholesterol plays an important role in the immune response [ 68 , 77 ]. Cholesterol is metabolized by cytochrome P450 enzymes (such as CYP7A1, CYP27A1, and CYP46A1), generating oxysterols with inflammatory (e.g., 7α-hydroxysterols and 27-hydroxysterols) or anti-inflammatory (e.g., 24-hydroxycholesterol) properties [ 78 , 79 ].…”