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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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 3,475
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
Flagged first, then by citations
1 of the 34 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 301–330 of 330
Bezine, M. (2017) · theses.fr (ABES) · doi:10.70675/a634c389z7b07z4830zb56dzbf7b53a56944 · Cited by 1
Contribution of Dietary Fat in Neuroinflammation
Farooqui, A. A. (2014) · Springer eBooks · doi:10.1007/978-3-319-04111-7_3
Sterol biosynthesis pathway is part of the interferon host defence response
Blanc, M. (2011) · ERA
Liver X receptors and immune regulation
Nunomura, S., Makishima, M., & Ra, C. (2010) · BioMolecular Concepts · doi:10.1515/bmc.2010.030
Immune response: Oxysterol takes Toll on IgA
Leah, E. (2010) · Lipidomics Gateway · doi:10.1038/lipidmaps.2010.1
Björkhem, I., Leoni, V., Meaney, S., & Besta, C. (2010)
Sterols and oxysterols in immune cell
Glass, C. K. (2013)
IJAR, Mohammed, Z., Saeed, H., & Nile, A. K. (2017) · International Journal of Advanced Research · doi:10.21474/ijar01/5302
Modulation of the Hedgehog Signaling Pathway by Sterol-based Small Molecules
Maschinot, C. A. (2018) · OpenCommons at University of Connecticut (University of Connecticut)
Chia, B. S. (2020) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Protection of eukaryotic cells against pore-forming toxins from pathogenic bacteria
Ormsby, T. J. R. (2021) · Cronfa (Swansea University) · doi:10.23889/suthesis.59035
Mueller, S. N. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733196177.793545765
Analysis of Sterols in Human T Helper Cells
Yutuc, E. (2017) · Cronfa (Swansea University) · doi:10.23889/suthesis.60641
The profiling and imaging of sterol molecules in the human brain
Griffiths, L. (2023) · Cronfa (Swansea University) · doi:10.23889/suthesis.62587
Toral-Ríos, D., Long, J. M., Ulrich, J. D., Yu, J., Strickland, M. R., Han, X., Holtzman, D. M., Cashikar, A. G., & Paul, S. M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.08.556884
Romero, J., Toral-Ríos, D., Yu, J., Paul, S. M., & Cashikar, A. G. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.09.561598
Zhou, S., Wen, X., Zhang, D., Li, D., Ding, C., Song, J., Huang, W., Jin, Z., Zhou, Z., Xia, X., et al. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4545261
Contribution of 25-hydroxycholesterol to the cross-interaction of the immune and nervous systems
Zakirjanova, G. F., Tsentsevitsky, A. N., Giniatullin, А. R., Nghomsi, S. M. F., Kuznetsova, E. A., & Petrov, A. M. (2023) · Genes and Cells · doi:10.23868/gc562791
Sterol Biomarker Discovery In Neurodegenerative Diseases
Pacciarini, M. (2023) · Cronfa (Swansea University) · doi:10.23889/suthesis.65375
Saito, H., Nishimura, M., Sato, R., & Yamauchi, Y. (2024) · BIO-PROTOCOL · doi:10.21769/bioprotoc.4924 · Cited by 1
Cholesterol Metabolism-Mediated Immune Regulation and Cancer ImmunotherapyPreprint
Zhang, J., Zhu, X., Han, L., Zhang, Z., Huang, X., Zhang, J., Li, J., Guo, C., & Yang, Q. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4760648
Vatanparast, R. G., Ghoflchi, S., Aliyari, M., Mohammadi, H., Yazdi, M., & Hosseini, H. (2026) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2026.107065
Liu, X., Gu, Y., Yang, Y., Li, X., Dai, Y., Zhang, R., Li, J., Chen, H. B., Zheng, Y., & Wu, R. (2026) · Microorganisms · doi:10.3390/microorganisms14040740
Rôle de LECT2 dans les maladies stéatosiques non alcooliques du foie
Pham, S. (2020) · theses.fr (ABES) · doi:10.70675/3693bfe6z9d91z4045za9a9zc37497dc9c1b
Mass Spectrometry-Based Screening Reveals Inhibitors of Cholesterol 25-Hydroxylase
Rahman, A., Hayes, E. H., & Adams, D. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.6c00385
Oxysterols in Cancer: From Biosynthesis and Pathophysiology to Targeted Therapeutics
Shang, H., & Li, Y. (2026) · MedComm – Oncology · doi:10.1002/mog2.70088
Macrophage-Derived 25-Hydroxycholesterol Drives Statin-Associated Acute Kidney InjuryPreprint
Wang, H. J., Kim, E. J., Cho, Y., Lee, J. H., Yoon, J., Kim, H.-Y., Jung, Y., Lee, H., Choi, H. Y., Lee, J.-Y., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.16.759612
Oral 25-Hydroxycholesterol Suppresses 4T1 Tumour Growth in an Immune-Context-Associated Manner
Liang, S., Xu, J., Wang, Z., Liu, Y., Xu, Y., Yao, C., & Zhu, Z. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27219735
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review