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Immunomodulatory effects of 25-hydroxyvitamin D3 on monocytic cell differentiation and influence of vitamin D3 polymorphisms in type 1 diabetes
- Source :
- The Journal of Steroid Biochemistry and Molecular Biology. 147:17-23
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Background Preventive measures and a causal therapy for type 1 diabetes (T1D) remain elusive. An imbalance between different dendritic cells (DC) with increased immunogenic DC and decreased tolerogenic DC (tDC) may lead to T1D. Furthermore, 25(OH)D 3 is associated with less adverse effects than 1,25(OH) 2 D 3 . Purpose The present study was performed to clarify the remaining issues about the cellular effects of 25(OH)D 3 in patients with T1D and the role of genetic polymorphisms of the vitamin D 3 (VD 3 ) metabolism on a functional cellular level. Materials and methods Twelve patients with T1D were case-matched to twelve healthy controls (HC). Monocytes (MC) were either not supplemented or supplemented with 25(OH)D 3 in vitro and phenotyped with fluorescence-activated cell sorting. In vitro synthesis and plasma levels of 25(OH)D 3 and 1,25(OH) 2 D 3 were analyzed as well as twelve gene polymorphisms of the VD 3 metabolism. Results 25(OH)D 3 significantly inhibited differentiation of MC into DC and led to an increase of intermediate cells (IC), which show a similar phenotype as tDC. The patient with a recent onset of T1D showed a higher increase in MC and IC compared to patients with long-standing T1D. There were significant differences for the increase of IC with supplementation of 25(OH)D 3 between different genotypes within the polymorphisms of VDR-BsmI-rs1544410, VDR-TaqI-rs731236 and CYP24A1-rs927650. Conclusion This study suggests that 25(OH)D 3 shows immunomodulatory effects on a cellular level in patients with T1D and HC by inhibiting the differentiation of MC into DC and promoting the formation of IC, which are similar to tDC, thereby shifting immunity to self-tolerance. The potency of 25(OH)D 3 did not differ between patients with T1D and HC. Increased plasma levels of 25(OH)D 3 may inhibit a proinflammatory cell milieu. Despite of the limited patient number, this study generates the hypothesis that the immunmodulatory effects may be influenced by genotypes of the VDR and CYP24A1 illustrating their functional role in T1D susceptibility, which is worth further investigation.
- Subjects :
- Adult
Male
Vitamin
medicine.medical_specialty
1303 Biochemistry
Adolescent
Endocrinology, Diabetes and Metabolism
Cellular differentiation
Clinical Biochemistry
Cell
610 Medicine & health
1308 Clinical Biochemistry
Biology
Biochemistry
Calcitriol receptor
Monocytes
Proinflammatory cytokine
1307 Cell Biology
Young Adult
chemistry.chemical_compound
Endocrinology
CYP24A1
Internal medicine
1312 Molecular Biology
medicine
Vitamin D and neurology
Humans
Immunologic Factors
Vitamin D3 24-Hydroxylase
Molecular Biology
Cholecalciferol
Polymorphism, Genetic
Dendritic Cells
Cell Biology
Cell Dedifferentiation
Middle Aged
In vitro
1310 Endocrinology
10021 Department of Trauma Surgery
2712 Endocrinology, Diabetes and Metabolism
Diabetes Mellitus, Type 1
medicine.anatomical_structure
chemistry
1313 Molecular Medicine
Immunology
Receptors, Calcitriol
Molecular Medicine
Female
Subjects
Details
- ISSN :
- 09600760
- Volume :
- 147
- Database :
- OpenAIRE
- Journal :
- The Journal of Steroid Biochemistry and Molecular Biology
- Accession number :
- edsair.doi.dedup.....b55e7aa93641393c9243f5cdc37f08e3