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High-dose vitamin D supplementation alters peripheral blood mononuclear cells transcriptomic in preschoolers with moderate to severe asthma

Year: 2026

Type: article

Abstract: Several studies have highlighted the potential role of vitamin D in modulating asthma severity, yet the underlying mechanisms are unclear. This study aimed to compare the effects of high-dose vitamin D3 supplementation on the transcriptomic-wide changes in peripheral blood mononuclear cells (PBMCs) of children with moderate to severe asthma. As part of an ongoing randomized controlled trial of children aged 1–5 years with asthma, we conducted an exploratory genetic study. Participants were allocated to receive either an oral bolus dose of 100,000IU vitamin D3 followed by daily supplementation of 400IU or placebo for 3.5 months. Blood samples were collected at baseline, 10 days, and 3.5 months; PBMCs gene expression profiling was performed using bulk RNA sequencing. The primary outcome was the change in PBMCs gene expression at 10 days. Forty-six children (54% male, median age: 2 years) were enrolled (vitamin D3: 24; placebo: 22). In the vitamin D group, differentially expressed genes included those involved in chemokine signaling ( CXCL10 , CCL22 , ACKR3 ), innate host defense ( DEFA1B , CAMP , LCN2 , RNASE3 ), and macrophage/cytokine regulation ( MRC1 , ZC3H12C , TNFRSF21 ). Furthermore, KEGG pathway analysis highlighted enrichment in immune and inflammatory pathways, including cytokine–cytokine receptor interaction, chemokine signaling, and antigen processing and presentation. However, after correcting for multiple testing, none of these changes remained statistically significant. High-dose vitamin D3 supplementation may modulate the expression of genes related to immune regulation and inflammation. Our findings provide a clear direction for further exploration in large-scale in vivo studies.

Source: Scientific Reports

DOI: 10.1038/s41598-026-79403-3