ArticlePloS one2012
Calcitriol modulates the CD46 pathway in T cells.
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 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Multiple sclerosis-associated CD226 variant disrupts vitamin D-induced type I Treg differentiation by impairing LFA-1 activation.The Journal of clinical investigation · 2026Article
- Reduced IL-10 production by FoxP3+IL-10+ Treg cells is partially compensated by complosome-associated induction of regulatory FoxP3-IL-10+ T cells in allergic eosinophilic asthma.Clinical and experimental immunology · 2026Article
- Transcriptomics identifies blunted immunomodulatory effects of vitamin D in people with multiple sclerosis.Scientific reports · 2024Article
- Low CD46 expression on activated CD4Frontiers in allergy · 2024Article
- Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications.Brain communications · 2022Review
- Cytokines and Transgenic Matrix in Autoimmune Diseases: Similarities and Differences.Biomedicines · 2020Review
- Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Multiple Sclerosis: Lipids, Lymphocytes, and Vitamin D.Immunometabolism · 2020Article
- Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis.Frontiers in immunology · 2020Article
- Environmental Influencers, MicroRNA, and Multiple Sclerosis.Journal of central nervous system disease · 2020Review
- Vitamin D and alopecia areata: possible roles in pathogenesis and potential implications for therapy.American journal of translational research · 2019Review
- Regulatory T Cells: From Discovery to Autoimmunity.Cold Spring Harbor perspectives in medicine · 2018Review
- Complement receptor CD46 co-stimulates optimal human CD8Nature communications · 2018Article
- CD46 is a potent co-stimulatory receptor for expansion of human IFN-γ-producing CD8Immunology letters · 2018Article
- Complement as a regulator of adaptive immunity.Seminars in immunopathology · 2018Review
- Genetic variation at the CD28 locus and its impact on expansion of pro-inflammatory CD28 negative T cells in healthy individuals.Scientific reports · 2017Article
- IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation.Brain : a journal of neurology · 2016Article
- Monocyte:T-cell interaction regulates human T-cell activation through a CD28/CD46 crosstalk.Immunology and cell biology · 2015Article
- Vitamin D Actions on CD4(+) T Cells in Autoimmune Disease.Frontiers in immunology · 2015Review
- Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis.Gastroenterology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)(2)D(3) or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFNγ ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS.
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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.