ArticlePloS one2012
Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Effect of egg consumption on inflammatory markers: a systematic review and meta-analysis of randomized controlled clinical trials.Journal of the science of food and agriculture · 2019Pooled it
- Trial
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- The impact of dyslipidemia on skeletal health - from an immunoregulatory perspective.Frontiers in immunology · 2026Review
- YDJC restrains Th1 cell differentiation by blocking SREBP2-mediated cholesterol biosynthesis to alleviate mucosal inflammation in inflammatory bowel disease.Cellular & molecular immunology · 2026Article
- Relationships Between Circulating Lipids, Lipoproteins, and Lymphocyte Subsets in the Multi-Ethnic Study of Atherosclerosis.Global heart · 2026Article
- Designer Solid Self-Emulsifying Nanovaccines Enable Dual Modulation of Dendritic Cells and T Cells for Potent Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Cholesterol promotesLife science alliance · 2024Article
- The influence of metabolic disorders on adaptive immunity.Cellular & molecular immunology · 2024Review
- The Role of Lipids in the Regulation of Immune Responses.Nutrients · 2023Review
- Lipid nanoparticles allow efficient and harmless ex vivo gene editing of human hematopoietic cells.Blood · 2023Article
- Hyperlipidaemia elicits an atypical, T helper 1-like CD4European heart journal open · 2023Article
- Low-density lipoprotein balances T cell metabolism and enhances response to anti-PD-1 blockade in a HCT116 spheroid model.Frontiers in oncology · 2023Article
- Trivalent chromium supplementation ameliorates adjuvant induced rheumatoid arthritis through up-regulation of FOXP3 and decrease in synovial Cathepsin G expression.Inflammopharmacology · 2022Article
- 2-Arachidonoylglycerol Reduces the Production of Interferon-Gamma in T Lymphocytes from Patients with Systemic Lupus Erythematosus.Biomedicines · 2022Article
- Ovarian Cancer Risk in Relation to Blood Cholesterol and Triglycerides.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Article
- The role of high-density lipoprotein in the regulation of the immune response: implications for atherosclerosis and autoimmunity.Immunology · 2021Review
- Targeting immunometabolism by active ingredients derived from traditional Chinese medicines for treatment of rheumatoid arthritis.Chinese herbal medicines · 2021Review
- Cholesterol metabolism: a new molecular switch to control inflammation.Clinical science (London, England : 1979) · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell signaling for T-cell growth, differentiation, and apoptosis is initiated in the cholesterol-rich microdomains of the plasma membrane known as lipid rafts. Herein, we investigated whether enrichment of membrane cholesterol in lipid rafts affects antigen-specific CD4 T-helper cell functions. Enrichment of membrane cholesterol by 40-50% following squalene administration in mice was paralleled by an increased number of resting CD4 T helper cells in periphery. We also observed sensitization of the Th1 differentiation machinery through co-localization of IL-2Rα, IL-4Rα, and IL-12Rβ2 subunits with GM1 positive lipid rafts, and increased STAT-4 and STAT-5 phosphorylation following membrane cholesterol enrichment. Antigen stimulation or CD3/CD28 polyclonal stimulation of membrane cholesterol-enriched, resting CD4 T-cells followed a path of Th1 differentiation, which was more vigorous in the presence of increased IL-12 secretion by APCs enriched in membrane cholesterol. Enrichment of membrane cholesterol in antigen-specific, autoimmune Th1 cells fostered their organ-specific reactivity, as confirmed in an autoimmune mouse model for diabetes. However, membrane cholesterol enrichment in CD4(+)Foxp3(+) T-reg cells did not alter their suppressogenic function. These findings revealed a differential regulatory effect of membrane cholesterol on the function of CD4 T-cell subsets. This first suggests that membrane cholesterol could be a new therapeutic target to modulate the immune functions, and second that increased membrane cholesterol in various physiopathological conditions may bias the immune system toward an inflammatory Th1 type response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.