25-Hydroxycholesterols in innate and adaptive immunity
Abstract
Cholesterol and components of the cholesterol biosynthetic pathway have fundamental roles in all mammalian cells. Hydroxylated forms of cholesterol are now emerging as important regulators of immune function. This involves effects on the cholesterol biosynthetic pathway and cell membrane properties, which can have antiviral and anti-inflammatory influences. In addition, a dihydroxylated form of cholesterol functions as an immune cell guidance cue by engaging the G protein-coupled receptor EBI2, and it is required for mounting adaptive immune responses. In this Review, we summarize the current understanding of the closely related oxysterols 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, and the growing evidence that they have wide-ranging influences on innate and adaptive immunity.
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25HC has antiviral properties and context-dependent immunomodulatory effects that can be proinflammatory or anti-inflammatory.
“25HC has been shown to have antiviral properties and exhibit context-dependent immunemodulatory effects which can be either proinflammatory or anti-inflammatory (12,13).”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [13]
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“nitrogen intermediates through NOS2 [135], and increased production of effectors such as cationic peptides, lysosomal hydrolases, and metabolic inhibitors [136], including itaconate (antibacterial) [107] and 25-hydroxycholesterol (antiviral) [137], all contribute to macrophage antimicrobial responses.”
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“25-HC has been described to have direct anti-viral effects, including inhibition of viral gene expression and altering of cellular cholesterol homeostasis to inhibit viral entry, assembly, and budding (Cyster et al., 2014).”
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- Authors
- Cyster, J. G., Dang, E. V., Reboldi, A., & Yi, T.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- Corresponding author
- Cyster, Jason G.
- Yi, Tangsheng
- Venue
- Nature Reviews Immunology
- Published
- 2014-10-17
- Volume
- 14
- Issue
- 11
- Pages
- 731-743
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W1970058349
- Cited by
- 388
- References
- 5
- Citations by year
- 2026: 32 · 2025: 34 · 2024: 37 · 2023: 40 · 2022: 30 · 2021: 45 · 2020: 32 · 2019: 31 · 2018: 24 · 2017: 35 · 2016: 31 · 2015: 16 · 2014: 1
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Asthma Foundation
- National Institute of Allergy and Infectious Diseases (AI40098)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Keywords
- 25-hydroxycholesterol, 7α,25-dihydroxycholesterol, oxysterols, cholesterol biosynthesis, innate immunity, adaptive immunity, antiviral activity, inflammation regulation, EBI2, G protein-coupled receptors, cell membrane properties
- MeSH terms
- Animals, Humans, Hydroxycholesterols, Immunity, Innate, Viruses, Receptors, G-Protein-Coupled, Mice, Sterol Regulatory Element Binding Proteins, Adaptive Immunity
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