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Oxysterols and the Immune Response: Implications in Non-communicable and Infectious...
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Oxysterols and the Immune Response: Implications in Non-communicable and Infectious Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 23015

Special Issue Editors

Dr. Gérard Lizard

E-Mail Website
Guest Editor
Team "Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism", Université de Bourgogne Franche-Comté, 21000 Dijon, France
Interests: lipids; oxysterols; fatty acids; polyphenols; oils; oxidation; inflammation; mitochondria; peroxisomes; lysosomes; apoptosis; autophagy; natural products; synthethic molecules; biomarkers; neurodegeneration; neurodegenerative diseases; aging; age-related diseases; nanoparticles; targeted therapy
Special Issues, Collections and Topics in MDPI journals
Dr. John J. Mackrill

E-Mail Website1 Website2
Guest Editor
Department of Physiology, School of Medicine, University College Cork, Western Gateway Building, Western Road, T12 XF62 Cork, Ireland
Dr. Tim Willinger

E-Mail Website
Guest Editor
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden

Special Issue Information

Dear Colleagues,

Oxysterols are cholesterol derivatives formed either by auto-oxidation, enzymatically, or by both mechanisms. The pro-inflammatory activities of oxysterols are widely suspected in chronic inflammatory diseases (cardiovascular disease, inflammatory bowel disease, hepatitis, allergy), as well as in frequent (multiple sclerosis, Alzheimer’s disease) and rare neurodegenerative diseases, such as peroxisomal disorders. Certain oxysterols can also act on bacteria, viruses, and parasites. Therefore, oxysterols are involved in the immune response and act directly or indirectly on infectious agents. The involvement of oxysterols in the immune response and cytokine storm is very likely, because receptors, such as TLRs, are associated with immune activities, and certain signaling pathways by which oxysterols promote cytokine production have been identified. This Special Issue will take into account reports dealing with these different aspects as well as pharmacological studies on molecules that modulate the biological activities of oxysterols in both infectious and non-communicable inflammatory diseases.

Dr. Gérard Lizard
Dr. John J. Mackrill
Dr. Tim Willinger
Guest Editor

Manuscript Submission Information

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Keywords

  • oxysterols
  • immune response
  • inflammation
  • autoimmunity
  • cytokine storm
  • chronic inflammatory diseases
  • infectious diseases
  • viruses
  • bacteria
  • parasites

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Published Papers (6 papers)

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Editorial

Jump to: Research, Review

4 pages, 241 KiB  
Editorial
Implication of Oxysterols in Infectious and Non-Communicable Inflammatory Diseases
by Gérard Lizard, John J. Mackrill and Tim Willinger
Cells 2023, 12(2), 241; https://doi.org/10.3390/cells12020241 - 6 Jan 2023
Viewed by 1336
Abstract
Oxysterols, derived from cholesterol oxidation, are formed either by autoxidation, via enzymes, or by both processes [...] Full article
(This article belongs to the Special Issue Oxysterols and the Immune Response: Implications in Non-communicable and Infectious Diseases)

Research

Jump to: Editorial, Review

18 pages, 4139 KiB  
Article
GPR183 Is Dispensable for B1 Cell Accumulation and Function, but Affects B2 Cell Abundance, in the Omentum and Peritoneal Cavity
by Line Barington, Liv von Voss Christensen, Kristian Kåber Pedersen, Kristine Niss Arfelt, Martin Roumain, Kristian Høj Reveles Jensen, Viktoria Madeline Skovgaard Kjær, Viktorija Daugvilaite, John F. Kearney, Jan Pravsgaard Christensen, Gertrud Malene Hjortø, Giulio G. Muccioli, Peter Johannes Holst and Mette Marie Rosenkilde
Cells 2022, 11(3), 494; https://doi.org/10.3390/cells11030494 - 31 Jan 2022
Cited by 3 | Viewed by 3843
Abstract
B1 cells constitute a specialized subset of B cells, best characterized in mice, which is abundant in body cavities, including the peritoneal cavity. Through natural and antigen-induced antibody production, B1 cells participate in the early defense against bacteria. The G protein-coupled receptor 183 [...] Read more.
B1 cells constitute a specialized subset of B cells, best characterized in mice, which is abundant in body cavities, including the peritoneal cavity. Through natural and antigen-induced antibody production, B1 cells participate in the early defense against bacteria. The G protein-coupled receptor 183 (GPR183), also known as Epstein-Barr virus-induced gene 2 (EBI2), is an oxysterol-activated chemotactic receptor that regulates migration of B cells. We investigated the role of GPR183 in B1 cells in the peritoneal cavity and omentum. B1 cells expressed GPR183 at the mRNA level and migrated towards the GPR183 ligand 7α,25-dihydroxycholesterol (7α,25-OHC). GPR183 knock-out (KO) mice had smaller omenta, but with normal numbers of B1 cells, whereas they had fewer B2 cells in the omentum and peritoneal cavity than wildtype (WT) mice. GPR183 was not responsible for B1 cell accumulation in the omentum in response to i.p. lipopolysaccharide (LPS)-injection, in spite of a massive increase in 7α,25-OHC levels. Lack of GPR183 also did not affect B1a- or B1b cell-specific antibody responses after vaccination. In conclusion, we found that GPR183 is non-essential for the accumulation and function of B1 cells in the omentum and peritoneal cavity, but that it influences the abundance of B2 cells in these compartments. Full article
(This article belongs to the Special Issue Oxysterols and the Immune Response: Implications in Non-communicable and Infectious Diseases)
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13 pages, 2195 KiB  
Article
Effect of Withanolide A on 7-Ketocholesterol Induced Cytotoxicity in hCMEC/D3 Brain Endothelial Cells
by Sandra Soh and Wei-Yi Ong
Cells 2022, 11(3), 457; https://doi.org/10.3390/cells11030457 - 28 Jan 2022
Cited by 6 | Viewed by 2514
Abstract
Withanolide A is a naturally occurring phytochemical that is found in Ashwagandha (Withania somnifera, fam. Solanaceae) or Indian Ginseng. In the current study, we elucidated the effect of withanolide A on 7-ketocholesterol (7KC) induced injury in hCMEC/D3 human brain endothelial cells. [...] Read more.
Withanolide A is a naturally occurring phytochemical that is found in Ashwagandha (Withania somnifera, fam. Solanaceae) or Indian Ginseng. In the current study, we elucidated the effect of withanolide A on 7-ketocholesterol (7KC) induced injury in hCMEC/D3 human brain endothelial cells. 7KC is a cholesterol oxidation product or oxysterol that is present in atherosclerotic plaques and is elevated in the plasma of patients with hypercholesterolemia and/or diabetes mellitus. Results showed that withanolide A significantly reduced the effects of 7KC, which include loss of endothelial cell viability, increase in expression of pro-inflammatory genes-IL-1β, IL-6, IL-8, TNF-α, cyclooxygenase-2 (COX-2), increased COX-2 enzyme activity, increased ROS formation, increased expression of inducible nitric oxide synthase and genes associated with blood clotting, including Factor 2/thrombin, Factor 8, von Willebrand factor, and thromboxane A synthase, and increased human thrombin enzyme activity. Some of the above effects of withanolide A on 7KC were reduced in the presence of the glucocorticoid receptor antagonist, mifepristone (RU486). These findings suggest that the glucocorticoid receptor could play a role in the cytoprotective, antioxidant, and anti-clotting effects of withanolide A against 7KC. Further studies are necessary to elucidate the detailed mechanisms of action of withanolide A against oxysterol-induced injury. Full article
(This article belongs to the Special Issue Oxysterols and the Immune Response: Implications in Non-communicable and Infectious Diseases)
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Review

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26 pages, 1096 KiB  
Review
Effects of Oxysterols on Immune Cells and Related Diseases
by Fábio Alessandro de Freitas, Débora Levy, Cadiele Oliana Reichert, Edecio Cunha-Neto, Jorge Kalil and Sérgio Paulo Bydlowski
Cells 2022, 11(8), 1251; https://doi.org/10.3390/cells11081251 - 7 Apr 2022
Cited by 19 | Viewed by 4756
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Oxysterols and the Immune Response: Implications in Non-communicable and Infectious Diseases)
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16 pages, 1786 KiB  
Review
Oxysterols in the Immune Response to Bacterial and Viral Infections
by Cheng Xiang Foo, Stacey Bartlett and Katharina Ronacher
Cells 2022, 11(2), 201; https://doi.org/10.3390/cells11020201 - 7 Jan 2022
Cited by 16 | Viewed by 3695
Abstract
Oxidized cholesterols, the so-called oxysterols, are widely known to regulate cholesterol homeostasis. However, more recently oxysterols have emerged as important lipid mediators in the response to both bacterial and viral infections. This review summarizes our current knowledge of selected oxysterols and their receptors [...] Read more.
Oxidized cholesterols, the so-called oxysterols, are widely known to regulate cholesterol homeostasis. However, more recently oxysterols have emerged as important lipid mediators in the response to both bacterial and viral infections. This review summarizes our current knowledge of selected oxysterols and their receptors in the control of intracellular bacterial growth as well as viral entry into the host cell and viral replication. Lastly, we briefly discuss the potential of oxysterols and their receptors as drug targets for infectious and inflammatory diseases. Full article
(This article belongs to the Special Issue Oxysterols and the Immune Response: Implications in Non-communicable and Infectious Diseases)
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27 pages, 14110 KiB  
Review
Multiple Targets for Oxysterols in Their Regulation of the Immune System
by Lisa Reinmuth, Cheng-Chih Hsiao, Jörg Hamann, Mette Rosenkilde and John Mackrill
Cells 2021, 10(8), 2078; https://doi.org/10.3390/cells10082078 - 13 Aug 2021
Cited by 12 | Viewed by 4659
Abstract
Oxysterols, or cholesterol oxidation products, are naturally occurring lipids which regulate the physiology of cells, including those of the immune system. In contrast to effects that are mediated through nuclear receptors or by epigenetic mechanism, which take tens of minutes to occur, changes [...] Read more.
Oxysterols, or cholesterol oxidation products, are naturally occurring lipids which regulate the physiology of cells, including those of the immune system. In contrast to effects that are mediated through nuclear receptors or by epigenetic mechanism, which take tens of minutes to occur, changes in the activities of cell-surface receptors caused by oxysterols can be extremely rapid, often taking place within subsecond timescales. Such cell-surface receptor effects of oxysterols allow for the regulation of fast cellular processes, such as motility, secretion and endocytosis. These cellular processes play critical roles in both the innate and adaptive immune systems. This review will survey the two broad classes of cell-surface receptors for oxysterols (G-protein coupled receptors (GPCRs) and ion channels), the mechanisms by which cholesterol oxidation products act on them, and their presence and functions in the different cell types of the immune system. Overall, this review will highlight the potential of oxysterols, synthetic derivatives and their receptors for physiological and therapeutic modulation of the immune system. Full article
(This article belongs to the Special Issue Oxysterols and the Immune Response: Implications in Non-communicable and Infectious Diseases)
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