ArticlePloS one2015
Vitamin D Antagonises the Suppressive Effect of Inflammatory Cytokines on CTLA-4 Expression and Regulatory Function.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Trial
- Vitamin D receptor (ApaI/BsmI) polymorphisms, human leukocyte antigen-DQB2/DRB3 sub-alleles, and endoplasmic reticulum stress: unravelling their interplay in the pathogenesis of Graves' disease in a tertiary care centre.Molecular biology reports · 2026Article
- Review
- Vitamin D affects antiphospholipid syndrome by regulating T cells (Review).International journal of molecular medicine · 2025Review
- Endocrine polyautoimmunity: Mechanistic insights and the future of AI-driven diagnostics.EXCLI journal · 2025Review
- Knowledge, Attitude and Practices Toward Vitamin D: A Cross-Sectional Study from Jordan.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2025Article
- Role of diet in development of non-communicable diseases: focus on gut microbiome.Central European journal of public health · 2024Review
- Aberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues.The Journal of allergy and clinical immunology · 2024Article
- Types of fiber and gut microbiota composition and diversity among arab females.Saudi journal of biological sciences · 2023Article
- Review
- Megalin and Vitamin D Metabolism-Implications in Non-Renal Tissues and Kidney Disease.Nutrients · 2022Review
- 1,25-Dihydroxyvitamin D3 suppresses CD4Immunology · 2022Article
- Pivotal role of vitamin D in mitochondrial health, cardiac function, and human reproduction.EXCLI journal · 2022Review
- Can vitamin D status influence seroconversion to SARS-COV2 vaccines?Frontiers in immunology · 2022Article
- Article
- Impaired Butyrate Induced Regulation of T Cell Surface Expression of CTLA-4 in Patients with Ulcerative Colitis.International journal of molecular sciences · 2021Article
- Article
- Vitamin D in the time of the coronavirus (COVID-19) pandemic - a clinical review from a public health and public mental health perspective.Therapeutic advances in psychopharmacology · 2021Review
- Maternal vitamin D supplementation inhibits bisphenol A-induced proliferation of Th17 cells in adult offspring.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2020Article
- Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
The immune suppressive protein CTLA-4 is constitutively expressed by Tregs and induced in effector T cells upon activation. Its crucial role in adaptive immunity is apparent from the fatal autoimmune pathology seen in CTLA-4 knockout mice. However, little is known regarding factors that regulate CTLA-4 expression and their effect upon its function to remove CD80 and CD86 from antigen presenting cells by transendocytosis. Th17 cells are emerging as significant players in autoimmunity as well as other diseases. Therefore, in this study we have examined the effects of Th17 polarising conditions on CTLA-4 expression and function in human T cells and show that Th17 conditions can suppress the expression of CTLA-4 and its transendocytic function. In contrast to Th17 cells, vitamin D is inversely associated with autoimmune disease. We have previously shown a striking ability of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) to enhance CTLA-4, however, its effects upon B7 transendocytosis and its activity in the context of inflammation remained unknown. Here we show that induction of CTLA-4 by 1,25(OH)2D3 can actually be enhanced in the presence of Th17 polarising cytokines. Furthermore, its transendocytic function was maintained such that T cells generated in the presence of Th17 conditions and 1,25(OH)2D3 were highly effective at capturing CTLA-4 ligands from antigen presenting cells and suppressing T cell division. Taken together, these data reveal an inhibitory effect of Th17 polarising conditions upon CTLA-4-mediated regulation and show that 1,25(OH)2D3 counteracts this effect. Given the importance of CTLA-4-mediated suppression in the control of autoimmune diseases, our novel data highlight the importance of vitamin D in inflammatory settings.
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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.