Effects of Oxysterols on Immune Cells and Related Diseases

Abstract

Oxysterols are the products of cholesterol oxidation. They have a wide range of effects on several cells, organs, and systems in the body. Oxysterols also have an influence on the physiology of the immune system, from immune cell maturation and migration to innate and humoral immune responses. In this regard, oxysterols have been involved in several diseases that have an immune component, from autoimmune and neurodegenerative diseases to inflammatory diseases, atherosclerosis, and cancer. Here, we review data on the participation of oxysterols, mainly 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, in the immune system and related diseases. The effects of these oxysterols and main oxysterol receptors, LXR and EBI2, in cells of the immune system (B cells, T cells, macrophages, dendritic cells, oligodendrocytes, and astrocytes), and in immune-related diseases, such as neurodegenerative diseases, intestinal diseases, cancer, respiratory diseases, and atherosclerosis, are discussed.

Estrogen contributes to sex differences in M2a macrophages during multi‐walled carbon nanotube‐induced respiratory inflammation

“…Sterols, specifically cholesterol and its oxidized derivatives—so‐called oxysterols, have also been implicated in the regulation of respiratory inflammation 50,88–91 . Moreover, cholesterol efflux and 25‐OHC are reported to be involved in M2 phenotype development, 36,43 a process which can be regulated by E 2 signaling 32–35 .…”

“…Sterols, specifically cholesterol and its oxidized derivatives-so-called oxysterols, have also been implicated in the regulation of respiratory inflammation. 50,[88][89][90][91] Moreover, cholesterol efflux and 25-OHC are reported to be involved in M2 phenotype development, 36,43 a process which can be regulated by E 2 signaling. [32][33][34][35] Combined, this research suggests that there are likely sex differences in cholesterol trafficking that could contribute to the observed sex differences in AM M2a phenotype following MWCNT exposure.…”

Cholesterol metabolism in the regulation of inflammatory responses

“…In contrast, increased 25-HC levels enhanced pro-inflammatory responses via an activator protein-1 (AP-1)-dependent increase in TLR expression in macrophages in the context of viral infections (Gold et al, 2014). As the present mini-review aims to provide a quick overview of the role of various cholesterol biosynthesis intermediates in inflammation, readers specifically interested in the role of the more extensively studied oxysterols are referred to comprehensive reviews (Bah et al, 2017;de Freitas et al, 2022).…”

Liver X Receptor Activation Attenuates Oxysterol-Induced Inflammatory Responses in Fetoplacental Endothelial Cells

“…They are generated mainly via chemical reactions involving reactive oxygen species (ROS) (e.g., 7-ketoC, 7β-OHC) and enzymatic reactions involving cytochrome P450 (e.g., 24-hydroxycholesterol, 27-hydroxycholesterol [ 22 ]. Oxysterols can bind to various receptors including LXR, C-X-C motif chemokine receptor 2 (CXCR2) and smoothened and can initiate a number of signaling pathways [ 23 ]. They are suggested to play a role in inflammatory diseases such as obesity, atherosclerosis, and neuro-inflammatory diseases [ 24 ].…”