Vitamin D2026

Exploratory multi-omics analysis suggests context-dependent immune responses to vitamin D supplementation in PBMCs of multiple sclerosis patients.

Tripathi Tanya, Gospodarska Emilia, Geran Rohat, Sperber Pia Sophie et al. — Frontiers in immunology

Summary

This study explored how vitamin D supplements affect the immune system in people with multiple sclerosis (MS). Researchers found that vitamin D didn't completely reprogram immune cells but caused specific changes in genes related to immunity, especially in those taking high doses. This suggests vitamin D's impact on the immune system is targeted and depends on the individual's health context.

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Key points

Vitamin D supplementation in multiple sclerosis patients led to specific, rather than widespread, changes in immune-related genes.
These changes were more pronounced in patients receiving high-dose vitamin D and involved genes linked to innate immunity and inflammation.
The study suggests that vitamin D's effects on the immune system are targeted and depend on the individual's health status.

What the study looked at

What question the study asked: Scientists know that low vitamin D levels are linked to multiple sclerosis (MS), but they wanted to understand precisely how vitamin D supplements affect the immune system at a genetic level in MS patients. They aimed to uncover the specific molecular changes that occur. How it was studied (design/participants): Researchers collected immune cells from the blood of MS patients, some of whom started high-dose vitamin D, others continued regular doses, and also from healthy individuals taking vitamin D. They then used advanced techniques (RNA sequencing to measure gene activity and ATAC sequencing to see which parts of DNA were accessible) to track changes in these cells over time. This allowed them to see how gene expression and DNA structure changed with vitamin D supplementation. What it found: The study found that vitamin D supplementation did not cause a complete overhaul of the immune system. Instead, it led to specific, targeted changes in certain immune-related genes, particularly those involved in the body's initial immune response and inflammation pathways. These changes were more noticeable in MS patients taking higher doses of vitamin D. The overall immune cell patterns in MS patients remained distinct from healthy individuals, suggesting vitamin D's effects are selective and depend on the individual's existing immune state.

Dietary takeaway

This research suggests that vitamin D plays a targeted role in modulating the immune system, especially in conditions like multiple sclerosis. While it doesn't call for a complete dietary overhaul, ensuring adequate vitamin D intake through fortified foods like milk and cereals, fatty fish, or supplements might support specific immune functions. Remember, this is one study, and more research is needed to provide definitive dietary recommendations for the general public or specific patient groups.

Abstract

INTRODUCTION: Vitamin D deficiency is a recognized risk factor for multiple sclerosis (MS), yet the molecular mechanisms linking vitamin D3 supplementation to immune regulation remain incompletely understood. METHODS: We performed longitudinal RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiling of peripheral blood mononuclear cells (PBMCs) from patients with relapsing-remitting MS who either initiated daily high-dose vitamin D3 supplementation or continued regular supplementation, alongside healthy individuals receiving monthly vitamin D3 bolus supplementation. Within-individual changes over the follow-up period were assessed and integrated with published THP-1-derived vitamin D receptor (VDR) binding datasets and previously validated vitamin D target genes. RESULTS: PBMCs from MS patients retained stable cohort-associated transcriptional and chromatin accessibility signatures that remained distinct from those of the healthy cohort. Vitamin D3 supplementation was not associated with global transcriptomic remodeling but was associated with changes in selected immune-regulatory gene expression programs. In the daily high-dose MS group, candidate genes showing longitudinal expression changes were enriched for innate immune sensing, Toll-like receptor signaling, cytokine-mediated communication, interferon-associated responses, and immune-cell differentiation. Candidate gene sets showed limited overlap across cohorts, although a subset of immune-regulatory and established vitamin D target genes was reproducibly identified. Chromatin accessibility profiling revealed thousands of cohort-specific differentially accessible regions, whereas supplementation-associated accessibility changes were comparatively modest. Integrative analysis prioritized a small set of candidate genes supported by multiple independent datasets, including , and . DISCUSSION: The findings suggest selective, context-dependent candidate molecular responses to vitamin D supplementation rather than global immune reprogramming. They also demonstrate the value of integrating transcriptomic and chromatin accessibility data to prioritize vitamin D-responsive pathways and genes for mechanistic validation in larger prospective and randomized studies.

View on PubMed →DOI: 10.3389/fimmu.2026.1845005