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

IntroductionVitamin D plays a vital role in modulating innate and adaptive immunity. This study investigated the gene regulatory mechanisms underlying this modulation in vivo.MethodsWe conducted a proof-of-principle intervention in which a participant received a bolus of vitamin D3 (80,000 IU) month...

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Main Authors: Tanya Tripathi, Carsten Carlberg
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559486/full
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author Tanya Tripathi
Carsten Carlberg
Carsten Carlberg
author_facet Tanya Tripathi
Carsten Carlberg
Carsten Carlberg
author_sort Tanya Tripathi
collection DOAJ
description IntroductionVitamin D plays a vital role in modulating innate and adaptive immunity. This study investigated the gene regulatory mechanisms underlying this modulation in vivo.MethodsWe conducted a proof-of-principle intervention in which a participant received a bolus of vitamin D3 (80,000 IU) monthly for three months. Peripheral blood mononuclear cells (PBMCs) were collected immediately before and at 4, 24, and 48 hours post-supplementation for transcriptome-wide differential gene expression analysis.ResultsWe identified 570 genes significantly responsive to vitamin D3 (p < 0.05) at one or more timepoints. In vitro experiments using PBMCs of the 0-hour time point of the same individual validated 303 of these as targets of the vitamin D receptor ligand 1α,25-dihydroxyvitamin D3. Among these, 55 primary target genes exhibited significant changes as early as 4 hours post-supplementation, including genes like SELENOS (selenoprotein S), which plays a key role in the selenium micronutrient network. Moreover, genes such as PRDX1 (peroxiredoxin 1), TXNRD1 (thioredoxin reductase 1), and SOD2 (superoxide dismutase 2), involved in antioxidant defense, were prominently regulated.DiscussionThese findings highlight a potential early and primary role for vitamin D in regulating detoxification processes, suggesting its critical involvement in maintaining redox homeostasis in immune cells of healthy individuals.
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spelling doaj-art-d0eea866976743c7bd4dba31c964d5bb2025-08-20T03:50:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15594861559486Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defenseTanya Tripathi0Carsten Carlberg1Carsten Carlberg2Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, PolandInstitute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, FinlandIntroductionVitamin D plays a vital role in modulating innate and adaptive immunity. This study investigated the gene regulatory mechanisms underlying this modulation in vivo.MethodsWe conducted a proof-of-principle intervention in which a participant received a bolus of vitamin D3 (80,000 IU) monthly for three months. Peripheral blood mononuclear cells (PBMCs) were collected immediately before and at 4, 24, and 48 hours post-supplementation for transcriptome-wide differential gene expression analysis.ResultsWe identified 570 genes significantly responsive to vitamin D3 (p < 0.05) at one or more timepoints. In vitro experiments using PBMCs of the 0-hour time point of the same individual validated 303 of these as targets of the vitamin D receptor ligand 1α,25-dihydroxyvitamin D3. Among these, 55 primary target genes exhibited significant changes as early as 4 hours post-supplementation, including genes like SELENOS (selenoprotein S), which plays a key role in the selenium micronutrient network. Moreover, genes such as PRDX1 (peroxiredoxin 1), TXNRD1 (thioredoxin reductase 1), and SOD2 (superoxide dismutase 2), involved in antioxidant defense, were prominently regulated.DiscussionThese findings highlight a potential early and primary role for vitamin D in regulating detoxification processes, suggesting its critical involvement in maintaining redox homeostasis in immune cells of healthy individuals.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559486/fullvitamin DtranscriptomePBMCsvitamin D target genesimmune systemdetoxification
spellingShingle Tanya Tripathi
Carsten Carlberg
Carsten Carlberg
Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense
Frontiers in Immunology
vitamin D
transcriptome
PBMCs
vitamin D target genes
immune system
detoxification
title Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense
title_full Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense
title_fullStr Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense
title_full_unstemmed Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense
title_short Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense
title_sort early in vivo target genes in human immune cells highlight vitamin d s role in antioxidant defense
topic vitamin D
transcriptome
PBMCs
vitamin D target genes
immune system
detoxification
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559486/full
work_keys_str_mv AT tanyatripathi earlyinvivotargetgenesinhumanimmunecellshighlightvitamindsroleinantioxidantdefense
AT carstencarlberg earlyinvivotargetgenesinhumanimmunecellshighlightvitamindsroleinantioxidantdefense
AT carstencarlberg earlyinvivotargetgenesinhumanimmunecellshighlightvitamindsroleinantioxidantdefense