The DOI matches its Crossref record; 33 of the 34 references it cites were found in a registry or an index.
25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production
Open accessAbstract
25-Hydroxycholesterol is produced in mammalian tissues. The function of this oxysterol is unknown. Here we describe a central role for 25-hydroxycholesterol in regulating the immune system. In initial experiments, we found that stimulation of macrophage Toll-like receptors (TLR) induced expression of cholesterol 25-hydroxylase and the synthesis of 25-hydroxycholesterol. Treatment of naïve B cells with nanomolar concentrations of 25-hydroxycholesterol suppressed IL-2-mediated stimulation of B cell proliferation, repressed activation-induced cytidine deaminase (AID) expression, and blocked class switch recombination, leading to markedly decreased IgA production. Consistent with these findings, deletion of the mouse cholesterol 25-hydroxylase gene caused an increase in serum IgA. Conversely, inactivation of the CYP7B1 oxysterol 7α-hydroxylase, which degrades 25-hydroxycholesterol, decreased serum IgA. The suppression of IgA class switching in B cells by a macrophage-derived sterol in response to TLR activation provides a mechanism for local and systemic negative regulation of the adaptive immune response by the innate immune system.
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“Mice lacking Ch25h appear to have a normal phenotype, show no changes in serum cytokine levels (Bauman et al., 2009), and have normal cholesterol metabolism (Reboldi et al., 2014).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Bauman et al., 2009
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“We and others have previously shown that Ch25h is responsible for the production and secretion of 25-HC by microglia (Bauman et al., 2009; Wong et al., 2020)”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Bauman et al., 2009
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“Ch25h, the enzyme that hydroxylates cholesterol to 25-hydroxycholesterol (25HC) (9) is markedly upregulated by toll-like receptor activation of macrophages (10,11).”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [10]
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“Mice lacking Ch25h appear to have a normal phenotype, show no changes in serum cytokine levels (Bauman et al., 2009), and have normal cholesterol metabolism (Reboldi et al., 2014).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Bauman et al., 2009
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Cites
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631
Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
Liu, P. T., Stenger, S., Li, H., Wenzel, L., Tan, B. H., Krutzik, S. R., Ochoa, M. T., Schauber, J., Wu, K., Meinken, C., et al. (2006) · Science · doi:10.1126/science.1123933 · Cited by 3,924
Muramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y., & Honjo, T. (2000) · Cell · doi:10.1016/s0092-8674(00)00078-7 · Cited by 3,559
Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
Serhan, C. N., Chiang, N., & Van Dyke, T. E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2294 · Cited by 2,932
Revy, P., Muto, T., Lévy, Y., Geissmann, F., Plebani, A., Sanal, Ö., Catalan, N., Forveille, M., Dufourcq-Lagelouse, R., Gennery, A. R., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)00079-9 · Cited by 1,645
An oxysterol signalling pathway mediated by the nuclear receptor LXRα
Janowski, B. A., Willy, P. J., Devi, T. R., Falck, J. R., & Mangelsdorf, D. J. (1996) · Nature · doi:10.1038/383728a0 · Cited by 1,591
Inferences, questions and possibilities in Toll-like receptor signalling
Beutler, B. (2004) · Nature · doi:10.1038/nature02761 · Cited by 1,476
Mechanism and Regulation of Class Switch Recombination
Stavnezer, J., Guikema, J. E. J., & Schrader, C. E. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090248 · Cited by 1,195
The immune geography of IgA induction and function
Macpherson, A. J., McCoy, K. D., Johansen, F.-E., & Brandtzaeg, P. (2007) · Mucosal Immunology · doi:10.1038/mi.2007.6 · Cited by 1,047
The regulation of IgA class switching
Cerutti, A. (2008) · Nature reviews. Immunology · doi:10.1038/nri2322 · Cited by 777
Cited by
Sorted by citations
Interferon-stimulated genes: A complex web of host defenses
Schneider, W. M., Chevillotte, M. D., & Rice, C. M. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120231 · Cited by 3,067
Microglial cell origin and phenotypes in health and disease
Saijo, K., & Glass, C. K. (2011) · Nature Reviews Immunology · doi:10.1038/nri3086 · Cited by 1,100
Liu, S.-Y., Aliyari, R., Chikere, K., Li, G., Marsden, M. D., Smith, J. K., Pernet, O., Guo, H., Nusbaum, R., Zack, J. A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.11.005 · Cited by 678
Oxysterols direct immune cell migration via EBI2
Hannedouche, S., Zhang, J., Yi, T., Shen, W., Nguyen, D. G., Pereira, J. P., Guerini, D., Baumgarten, B. U., Roggo, S. P., Wen, B. G., et al. (2011) · Nature · doi:10.1038/nature10280 · Cited by 509
Quehenberger, O., & Dennis, E. A. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1104901 · Cited by 470
Metadata
- Authors
- Bauman, D. R., Bitmansour, A. D., McDonald, J. G., Thompson, B. M., Liang, G., & Russell, D. W.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Department of Molecular Genetics and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-09-29
- Volume
- 106
- Issue
- 39
- Pages
- 16764-16769
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2757821
- OpenAlex
- W2038363528
- Cited by
- 329
- References
- 34
- Citations by year
- 2026: 15 · 2025: 10 · 2024: 19 · 2023: 26 · 2022: 16 · 2021: 21 · 2020: 30 · 2019: 28 · 2018: 27 · 2017: 19 · 2016: 21 · 2015: 13 · 2014: 19 · 2013: 18 · 2012: 21
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Welch Foundation (I-0971)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 20848)
- National Institute of General Medical Sciences (U54GM069338, GM 069338)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 07745, T32DK007745)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- 25-hydroxycholesterol, oxysterols, macrophages, Toll-like receptor activation, immunoglobulin A, class switch recombination, activation-induced cytidine deaminase, B cell proliferation, cholesterol 25-hydroxylase, CYP7B1, negative regulation of immune response
- MeSH terms
- Animals, B-Lymphocytes, Hydroxycholesterols, Immunoglobulin A, Macrophages, Mice, Transgenic, Steroid Hydroxylases, Cytokines, Toll-Like Receptors, Mice
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