Publications

Mariusz Jankowski, Emmi Hämäläinen, Mari Taipale, Sami Heikkinen & Carsten Carlberg

Vitamin D and lipopolysaccharide jointly induce a distinct epigenetic and transcriptional program in human monocytes

Scientific Reports volume 15, Article number: 27480 (2025)

Pathogen-associated molecular patterns such as lipopolysaccharide (LPS) mimic immune responses triggered by bacterial infections. The hormonally active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], supports innate immunity, but its molecular mechanisms remain incompletely understood. We investigated epigenomic and transcriptomic changes in THP-1 monocytes that were either unprimed or primed for 24 h with 1,25(OH)2D3 or LPS, followed by a second 24-hour stimulation with 1,25(OH)2D3, LPS, or their combination. Epigenome profiling via ATAC-seq revealed that co-stimulation with 1,25(OH)2D3 and LPS induces substantially more chromatin accessibility changes than either treatment alone, with up to 81% of altered regions uniquely responsive to the combination. Motif enrichment analysis highlighted JUN/FOS transcription factors as key regulators of this synergistic response. Transcriptomic analysis via RNA-seq mirrored these findings, though fewer genes than chromatin regions were affected. Notably, under 1,25(OH)2D3-primed conditions, 331 genes exhibited synergistic expression changes upon co-treatment, meaning that their responses significantly deviates from the additive effects of the individual stimulations. This includes 264 genes previously unrecognized as vitamin D targets. Functional annotation revealed that these genes are primarily linked to monocyte and T cell differentiation, in contrast to classical vitamin D targets associated with inflammation. In conclusion, our findings provide mechanistic insight into how vitamin D modulates inflammation through epigenetic and transcriptional reprogramming.

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Tanya Tripathi, Carsten Carlberg

Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense

Frontiers in Immunology

Vitamin D3 is a vital micronutrient that can either be synthesized endogenously in the skin upon exposure to UV-B radiation or obtained through dietary sources and supplementation. One of the most ancient evolutionary roles of vitamin D is maintaining energetic and survival homeostasis, such as detoxification. However, its most well-known physiological function is regulating calcium homeostasis, which is crucial for bone mineralization. Beyond these roles, vitamin D also plays a critical part in modulating the immune system. It supports the innate immune response to infectious diseases, such as tuberculosis and COVID-19 (coronavirus disease), while also preventing overactivation of the adaptive immune system. This dual function is essential for reducing the risk of autoimmune diseases, such as multiple sclerosis, and for mitigating severe immune responses, such as those observed in critical cases of COVID-19.

Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense [PDF]

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Emilia Gospodarska, Ranjini Ghosh Dastidar, Julia Jaroslawska, Maciej Rybiński,Marianna Raczyk, Kornelia Tokarczyk-Malesa, Jerzy Romaszko2 & Carsten Carlberg

Transcriptomic profiling of immune modulation induced by vitamin D3 in the VitDPAS and VitDHiD cohort studies

Scientific Reports

The VitDPAS study (NCT06104111) was designed as a medical experiment to assess the in vivo effects of vitamin D on immune responses. This study enrolled 45 healthy individuals from Olsztyn, Poland, who received a body weight-adjusted bolus dose of vitamin D3 (1,000 IU/kg). Transcriptome-wide differential gene expression analysis of peripheral blood mononuclear cells, collected before and 24 h after supplementation, identified 758 significantly responsive genes (p < 0.05). By correlating individual gene expression changes with alterations in vitamin D status, participants were categorized into three response groups: 17 high responders, 19 mid responders, and 9 low responders. A comparative analysis with the VitDHiD study (NCT03537027), conducted on a Finnish cohort of 25 healthy participants, revealed 232 overlapping target genes, enabling an integrated assessment of vitamin D responsiveness across all 70 individuals. Applying a more stringent statistical threshold (false discovery rate < 0.05) highlighted 26 shared target genes, demonstrating a consistent in vivo response to vitamin D3 across both cohorts. The modulation of inflammatory processes, mediated primarily via tumor necrosis factor and nuclear factor κB signaling pathways, emerged as a shared effect, highlightening the immunomodulatory potential of vitamin D as a key function of the vitamin in healthy individuals.

Transcriptomic profiling of immune modulation induced by vitamin D3 in the VitDPAS and VitDHiD cohort studies [PDF]

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Parcival Maissan, Carsten Carlberg

Circadian Regulation of Vitamin D Target Genes Reveals a Network Shaped by Individual Responsiveness

Nutrients 2025, 17(7), 1204

As part of the VitDHiD intervention study, we identified 87 in vivo vitamin D target genes with circadian expression patterns in immune cells, forming a regulatory network centered on transcription factors and membrane receptors. These genes exhibit a narrow basal expression range, with 80% downregulated upon vitamin D₃ supplementation. Clustering analysis revealed six distinct gene groups, with the two most prominent clusters driven by the transcription factor CSRNP1 (cysteine- and serine-rich nuclear protein 1) and GAS7 (growth arrest-specific 7), a known differentiation inducer. Among the 25 VitDHiD study participants, we identified two subgroups distinguished by significant differences in the responsiveness of 14 in vivo vitamin D target genes. These genes encode transcription factors like CSRNP1, as well as metabolic enzymes and transporters, including NAMPT (nicotinamide phosphoribosyltransferase), PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3), and SLC2A3 (solute carrier family 2 member 3). Notably, all 14 genes possess a vitamin D receptor-binding enhancer within a reasonable distance of their transcription start site.

Circadian Regulation of Vitamin D Target Genes Reveals a Network Shaped by Individual Responsiveness [PDF]

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