Endocrine Abstracts

Dysregulated T helper cells and vitamin D (VD) deficiency are important factors in the pathogenesis of Type 1 diabetes mellitus (T1D). Therefore, we investigated the immune effects of high dose VD-treatment on gene expression (GE) pattern in T helper cells (Th) before and after VD-therapy in patients with T1D.

Methods: Seven T1D patients with 25(OH)D₃ levels below 20 ng/ml received 3 months 4000 IU/d Vigantol oil. The 25(OH)D₃ plasma concentration (using radioimmunoassay) and GE within Th cells (using GeneChip) were measured at baseline (V1) after 3 months treatment (V3). VD-therapy effects on the GE were evaluated using the differences between V1 and V3 (expressed in fold changes=FC) by the statistical computing environment R version 3.0.2.

Results: The 25(OH)D₃ concentration increased in median from 14 to 38 ng/ml (P=0.02) after high dose VD. Furthermore, 48 annotated genes changed significantly in Th cells of patients with T1D after VD supplementation. Important to note, unique four genes that code for dual specificity phosphatase 2 (=DUSP2/FC:1.4; P=0.05), HAUS augmin-like complex, subunit 2 (=HAUS2/FC:1.3; P=0.01), jun B proto-oncogene (=JUNB/FC:1.6; P=0.04) and mannose-P-dolichol utilization defect 1 (=MPDU1/FC:1.4; P=0.02) showed a higher expression after VD treatment, in T1D patients. In contrast, 44 genes were down regulated: exemplarily, genes which code for interferon receptor 1 (=IFNAR1/FC: −1.3; P=0.02), nuclear distribution protein (=NUDC FC: −1.3; P=0.04) and zinc finger protein 830 (=ZNF830 FC: −1.4; P=0.02).

Conclusion: The elevation of 25(OH)D₃ induced by Vigantol therapy (4000 IU/day) leads to differential GE pattern in Th cells from T1D patients (four genes upregulated/44 genes down regulated). The Th cell response to vitamin D results in an upregulated gene set (DUSP2, HAUS2, JUNB, MPDU1) and a downregulated gene set (IFNAR1, NUDC, ZNF830). Our data suggest an indirect VD effect on both gene sets via activation of transcription factors such as activator protein 1 (AP-1) and signal transducer and activator and transcription family members (Stat1 and Stat3), respectively.