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Transcriptomics identifies blunted immunomodulatory effects of
Scientific Reports - Transcriptomics identifies blunted immunomodulatory effects of vitamin D in people with multiple sclerosis
  • Yeh, W. Z. et al. Immunoregulatory effects and therapeutic potential of vitamin D in multiple sclerosis. Br. J. Pharmacol. 177, 4113–4133 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Veldman, C. M., Cantorna, M. T. & DeLuca, H. F. Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system. Arch. Biochem. Biophys. 374, 334–338 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Booth, D. R. et al. Cistromic and genetic evidence that the vitamin D receptor mediates susceptibility to latitude-dependent autoimmune diseases. Genes Immun. 17, 213–219 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baeke, F. et al. Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D3 in the immune system. J. Steroid Biochem. Mol. Biol. 121, 221–227 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Liu, P. T., Stenger, S., Tang, D. H. & Modlin, R. L. Cutting edge: Vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J. Immunol. 179, 2060–2063 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Penna, G. & Adorini, L. 1α,25-Dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol. 164, 2405–2411 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Jeffery, L. E. et al. 1,25-dihydroxyvitamin D3 and interleukin-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J. Immunol. 183, 5458–5467 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Prietl, B. et al. High-dose cholecalciferol supplementation significantly increases peripheral CD4+ Tregs in healthy adults without negatively affecting the frequency of other immune cells. Eur. J. Nutr. 53, 751–759 (2014).

    Article  CAS  PubMed  Google Scholar 

  • Allen, A. C. et al. A pilot study of the immunological effects of high-dose vitamin D in healthy volunteers. Mult. Scler. 18, 1797–1800 (2012).

    Article  PubMed  Google Scholar 

  • Munger, K. L., Levin, L. I., Hollis, B. W., Howard, N. S. & Ascherio, A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296, 2832–2838 (2006).

    Article  CAS  PubMed  Google Scholar 

  • da Costa, D. S. M. M. et al. Vitamin D modulates different IL-17-secreting T cell subsets in multiple sclerosis patients. J. Neuroimmunol. 299, 8–18 (2016).

    Article  PubMed  Google Scholar 

  • Kickler, K., Ni Choileain, S., Williams, A., Richards, A. & Astier, A. L. Calcitriol modulates the CD46 pathway in T cells. PLoS One 7, e48486 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jagannath, V. A. et al. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD008422.pub3 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  • Hupperts, R. et al. Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a. Neurology https://doi.org/10.1212/WNL.0000000000008445 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  • Subramanian, A. et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. 102, 15545–15550 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science 365, eaav7188 (2019).

    Article  PubMed Central  Google Scholar 

  • Zhang, B. & Horvath, S. A general framework for weighted gene co-expression network analysis. Stat. Appl. Genet. Mol. Biol. 4, 17 (2005).

    Article  MathSciNet  Google Scholar 

  • Langfelder, P. & Horvath, S. Eigengene networks for studying the relationships between co-expression modules. BMC Syst. Biol. 1, 54 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  • Kriegler, M., Perez, C., DeFay, K., Albert, I. & Lu, S. D. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: Ramifications for the complex physiology of TNF. Cell 53, 45–53 (1988).

    Article  CAS  PubMed  Google Scholar 

  • Calzascia, T. et al. TNF-α is critical for antitumor but not antiviral T cell immunity in mice. J. Clin. Investig. 117, 3833–3845 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park, K. M. & Bowers, W. J. Tumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction. Cell Signal. 22, 977–983 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schioppa, T. et al. B regulatory cells and the tumor-promoting actions of TNF-α during squamous carcinogenesis. Proc. Natl. Acad. Sci. 108, 10662–10667 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharief, M. K. & Hentges, R. Association between tumor necrosis factor-α and disease progression in patients with multiple sclerosis. N. Engl. J. Med. 325, 467–472 (1991).

    Article  CAS  PubMed  Google Scholar 

  • Rieckmann, P. et al. Tumor necrosis factor-α messenger RNA expression in patients with relapsing-remitting multiple sclerosis is associated with disease activity. Ann. Neurol. 37, 82–88 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Huang, W.-X., Huang, P., Link, H. & Hillert, J. Cytokine analysis in multiple sclerosis by competitive RT-PCR: A decreased expression of IL-10 and an increased expression of TNF-α in chronic progression. Mult. Scler. 5, 342–348 (1999).

    CAS  PubMed  Google Scholar 

  • van Oosten, B. W. et al. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47, 1531–1534 (1996).

    Article  PubMed  Google Scholar 

  • Arnett, H. A. et al. TNFα promotes proliferation of oligodendrocyte progenitors and remyelination. Nat. Neurosci. 4, 1116–1122 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Müller, K. et al. 1,25-dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level. Cytokine 4, 506–512 (1992).

    Article  PubMed  Google Scholar 

  • Lysandropoulos, A. P. et al. Vitamin D has a direct immunomodulatory effect on CD8+ T cells of patients with early multiple sclerosis and healthy control subjects. J. Neuroimmunol. 233, 240–244 (2011).

    Article  CAS  PubMed  Google Scholar 

  • Peterson, C. A. & Heffernan, M. E. Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. J. Inflamm. 5, 10 (2008).

    Article  Google Scholar 

  • Yang, W. S. et al. 1,25-Dihydroxyvitamin D3 causes ADAM10-dependent ectodomain shedding of tumor necrosis factor receptor 1 in vascular smooth muscle cells. Mol. Pharmacol. 87, 533–542 (2015).

    Article  PubMed  Google Scholar 

  • Song, G. G., Bae, S.-C. & Lee, Y. H. Association between vitamin D intake and the risk of rheumatoid arthritis: A meta-analysis. Clin. Rheumatol. 31, 1733–1739 (2012).

    Article  PubMed  Google Scholar 

  • Ananthakrishnan, A. N. et al. Higher predicted vitamin d status is associated with reduced risk of Crohn’s disease. Gastroenterology 142, 482–489 (2012).

    Article  CAS  PubMed  Google Scholar 

  • Kamen, D. L. et al. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun. Rev. 5, 114–117 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Umar, M. et al. Vitamin D and the pathophysiology of inflammatory skin diseases. SPP 31, 74–86 (2018).

    CAS  Google Scholar 

  • Hahn, J. et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ 376, e066452 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  • Dimitrov, V. et al. Vitamin D-regulated gene expression profiles: Species-specificity and cell-specific effects on metabolism and immunity. Endocrinology 162, bqaa218 (2021).

    Article  PubMed  Google Scholar 

  • von Essen, M. R. et al. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat. Immunol. 11, 344–349 (2010).

    Article  Google Scholar 

  • Richards, J. B. et al. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am. J. Clin. Nutr. 86, 1420–1425 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Jirmanova, L., Giardino Torchia, M. L., Sarma, N. D., Mittelstadt, P. R. & Ashwell, J. D. Lack of the T cell-specific alternative p38 activation pathway reduces autoimmunity and inflammation. Blood 118, 3280–3289 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y. et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J. Immunol. 188, 2127–2135 (2012).

    Article  CAS  PubMed  Google Scholar 

  • Ding, C., Wilding, J. P. H. & Bing, C. 1,25-Dihydroxyvitamin D3 protects against macrophage-induced activation of NFκB and MAPK signalling and chemokine release in human adipocytes. PLoS One 8, e61707 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xin, L. et al. 1,25-Dihydroxy vitamin D3 attenuates the oxidative stress-mediated inflammation induced by PM2.5 via the p38/NF-κB/NLRP3 pathway. Inflammation 42, 702–713 (2019).

    Article  CAS  PubMed  Google Scholar 

  • Joshi, S. et al. 1,25-Dihydroxyvitamin D3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol. Cell. Biol. 31, 3653–3669 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeuchi, A. et al. Nuclear factor of activated T cells (NFAT) as a molecular target for 1α,25-dihydroxyvitamin D3-mediated effects. J. Immunol. 160, 209–218 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Matilainen, J. M., Räsänen, A., Gynther, P. & Väisänen, S. The genes encoding cytokines IL-2, IL-10 and IL-12B are primary 1α,25(OH)2D3 target genes. J. Steroid Biochem. Mol. Biol. 121, 142–145 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Alroy, I., Towers, T. L. & Freedman, L. P. Transcriptional repression of the interleukin-2 gene by vitamin D3: Direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. Mol. Cell. Biol. 15, 5789–5799 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ikeda, U. et al. 1α,25-Dihydroxyvitamin D3 and all-trans retinoic acid synergistically inhibit the differentiation and expansion of Th17 cells. Immunol. Lett. 134, 7–16 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Palmer, M. T. et al. Lineage-specific effects of 1,25-dihydroxyvitamin d3 on the development of effector CD4 T cells. J. Biol. Chem. 286, 997–1004 (2011).

    Article  CAS  PubMed  Google Scholar 

  • Müller, K., Ødum, N. & Bendtzen, K. 1,25-Dihydroxyvitamin D3 selectively reduces interleukin-2 levels and proliferation of human T cell lines in vitro. Immunol. Lett. 35, 177–182 (1993).

    Article  PubMed  Google Scholar 

  • Urry, Z. et al. The role of 1α,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3+ and IL-10+ CD4+ T cells. Eur. J. Immunol. 42, 2697–2708 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chauss, D. et al. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells. Nat. Immunol. 23, 62–74 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Bhargava, P. et al. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls. Mult. Scler. 22, 753–760 (2016).

    Article  CAS  PubMed  Google Scholar 

  • Bhargava, P., Fitzgerald, K. C., Calabresi, P. A. & Mowry, E. M. Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation. JCI Insight 2, e95302 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  • Lu, M., Shi, H., Taylor, B. V. & Körner, H. Alterations of subset and cytokine profile of peripheral T helper cells in PBMCs from Multiple Sclerosis patients or from individuals with MS risk SNPs near genes CYP27B1 and CYP24A1. Cytokine 153, 155866 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Mu, Z. et al. The impact of cell type and context-dependent regulatory variants on human immune traits. Genome Biol. 22, 122 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ewing, E. et al. Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression. EBioMedicine 43, 411–423 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim, D. et al. Peripheral T-cells, B-cells, and monocytes from multiple sclerosis patients supplemented with high-dose vitamin d show distinct changes in gene expression profiles. Nutrients 14, 4737 (2022).

    Article  MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  • Polman, C. H. et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann. Neurol. 69, 292–302 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  • Andrews, S. FastQC: A Quality Control Tool for High Throughput Sequence Data (2010).

  • Bray, N. L., Pimentel, H., Melsted, P. & Pachter, L. Near-optimal probabilistic RNA-seq quantification. Nat. Biotechnol. 34, 525–527 (2016).

    Article  CAS  PubMed  Google Scholar 

  • R Core Team. R: A Language and Environment for Statistical Computing (2019).

  • Soneson, C., Love, M. I. & Robinson, M. D. Differential analyses for RNA-seq: Transcript-level estimates improve gene-level inferences. F1000Res 4, 1521 (2016).

    Article  PubMed Central  Google Scholar 

  • Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Risso, D., Ngai, J., Speed, T. P. & Dudoit, S. Normalization of RNA-seq data using factor analysis of control genes or samples. Nat. Biotechnol. 32, 896–902 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eisenberg, E. & Levanon, E. Y. Human housekeeping genes, revisited. Trends Genet. 29, 569–574 (2013).

    Article  CAS  PubMed  Google Scholar 

  • Ramagopalan, S. V. et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution. Genome Res. 20, 1352–1360 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neme, A., Seuter, S. & Carlberg, C. Selective regulation of biological processes by vitamin D based on the spatio-temporal cistrome of its receptor. Biochim. Biophys. Acta (BBA) Gene Regul. Mech. 1860, 952–961 (2017).

    Article  CAS  Google Scholar 

  • Shirvani, A., Kalajian, T. A., Song, A. & Holick, M. F. Disassociation of vitamin D’s calcemic activity and non-calcemic genomic activity and individual responsiveness: A randomized controlled double-blind clinical trial. Sci. Rep. 9, 17685 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  • Gandolfo, L. C. & Speed, T. P. RLE plots: Visualizing unwanted variation in high dimensional data. PLoS One 13, e0191629 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  • Cunningham, F. et al. Ensembl 2022. Nucleic Acids Res. 50, D988–D995 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Durinck, S., Spellman, P. T., Birney, E. & Huber, W. Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat. Protoc. 4, 1184–1191 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lun, A. T. L., Chen, Y. & Smyth, G. K. It’s DE-licious: A recipe for differential expression analyses of RNA-seq experiments using quasi-likelihood methods in edgeR. In Statistical Genomics: Methods and Protocols (eds Mathé, E. & Davis, S.) 391–416 (Springer, 2016). https://doi.org/10.1007/978-1-4939-3578-9_19.

    Chapter  Google Scholar 

  • Evelo, C. et al. Vitamin D metabolism (Homo sapiens)—WikiPathways. https://www.wikipathways.org/index.php/Pathway:WP1531

  • Langfelder, P. & Horvath, S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinform. 9, 559 (2008).

    Article  Google Scholar 

  • Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B (Methodology) 57, 289–300 (1995).

    MathSciNet  Google Scholar 

  • Liberzon, A. et al. Molecular signatures database (MSigDB) 3.0. Bioinformatics 27, 1739–1740 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27–30 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu, T. et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation 2, 100141 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wickham, H. ggplot2 (Springer International Publishing, 2016). https://doi.org/10.1007/978-3-319-24277-4.

    Book  Google Scholar 

  • Chen, J., Bardes, E. E., Aronow, B. J. & Jegga, A. G. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 37, W305–W311 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847–2849 (2016).

    Article  CAS  PubMed  Google Scholar 

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