ArticleImmunity2021
The cholesterol metabolite 25-hydroxycholesterol restrains the transcriptional regulator SREBP2 and limits intestinal IgA plasma cell differentiation.
Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
- Article
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- METTL16 Promotes Head and Neck Squamous Cell Carcinoma Progression via m6A-Mediated Stabilization of SREBP2 mRNA and Enhanced Cholesterol Biosynthesis.Cancer medicine · 2026Article
- Spatial instruction of tissue immunity.ImmunoHorizons · 2026Review
- Targeting cholesterol-driven immunometabolism in cancer: from molecular circuits to clinical translation.Molecular cancer · 2026Review
- Why are long-lived plasma cells long-lived?Frontiers in immunology · 2026Review
- 25HC regulates the polarization of CD163Frontiers in immunology · 2026Article
- OSBPL3-driven sterol metabolic reprogramming promotes oncogenic signaling and therapeutic resistance in pancreatic cancer.Theranostics · 2026Article
- Dynamic regulatory mechanism of cholesterol 25-hydroxylase-mediated antiviral response in RNA virus infections.Frontiers in cellular and infection microbiology · 2026Review
- Tandospirone augments cisplatin treatment by lowering cholesterol and managing distress in NSCLC patients.NPJ digital medicine · 2025Article
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- Oxysterol-Induced Inflammation in Human Diseases: Strategies for Treatment with Natural Compounds and Synthetic Molecules.Molecules (Basel, Switzerland) · 2025Review
- Obesity reshapes regulatory T cells in the visceral adipose tissue by disrupting cellular cholesterol homeostasis.Science immunology · 2025Article
- Novel insights and an updated review of metabolic syndrome in immune-mediated organ transplant rejection.Frontiers in immunology · 2025Review
- Metabolic collusion driving immune evasion in cholangiocarcinoma: unmasking the dual control of the immuno-metabolic microenvironment.Frontiers in immunology · 2025Review
- StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation.Biochemistry and biophysics reports · 2024Article
- Cholesterol sensing and metabolic adaptation in tissue immunity.Trends in immunology · 2024Review
- All roads lead to IgA: Mapping the many pathways of IgA induction in the gut.Immunological reviews · 2024Review
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Diets high in cholesterol alter intestinal immunity. Here, we examined how the cholesterol metabolite 25-hydroxycholesterol (25-HC) impacts the intestinal B cell response. Mice lacking cholesterol 25-hydroxylase (CH25H), the enzyme generating 25-HC, had higher frequencies of immunoglobulin A (IgA)-secreting antigen-specific B cells upon immunization or infection. 25-HC did not affect class-switch recombination but rather restrained plasma cell (PC) differentiation. 25-HC was produced by follicular dendritic cells and increased in response to dietary cholesterol. Mechanistically, 25-HC restricted activation of the sterol-sensing transcription factor SREBP2, thereby regulating B cell cholesterol biosynthesis. Ectopic expression of SREBP2 in germinal center B cells induced rapid PC differentiation, whereas SREBP2 deficiency reduced PC output in vitro and in vivo. High-cholesterol diet impaired, whereas Ch25h deficiency enhanced, the IgA response against Salmonella and the resulting protection from systemic bacterial dissemination. Thus, a 25-HC-SREBP2 axis shapes the humoral response at the intestinal barrier, providing insight into the effect of high dietary cholesterol in intestinal immunity.
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