1,25-Dihydroxyvitamin D3 (vitD3) is an immunoregulatory hormone with beneficial effects on Th1 mediated autoimmune diseases. Although the inhibitory effects of vitD3 on macrophages and dendritic cells are well documented, any direct effects of vitD3 on Th cell development are not clearly defined.
We demonstrated that vitD3 affects Th cell polarization by inhibiting Th1 (IFN- production) and augmenting Th2 cell development (IL-4, IL-5, and IL-10 production).
An increased expression of the Th2-specific transcription factors GATA-3 and c-maf correlated with the increased production of Th2 cytokines after vitD3 treatment. The vitD3-induced effects were largely mediated via IL-4, because neutralization of IL-4 almost completely abrogated the augmented Th2 cell development after vitD3 treatment.
1,25-Dihydroxyvitamin D3 (vitD3)3 is a seco-steroid hormone that is not only involved in mineral and skeletal homeostasis, but also regulates the differentiation, growth, and function of a broad range of cells, including cells of the immune system (20). VitD3 acts through its receptor, the nuclear vitD3 receptor, which in turn acts as a transcription factor by binding to distinct vitD3 receptor responsive elements that are present in the promoter regions of target genes. VitD3 also modulates gene transcription by affecting the activity of transcription factors,
Furthermore, vitD3 has been demonstrated to prevent Th1-mediated autoimmune diseases in animal models for experimental allergic encephalomyelitis, systemic lupus erythematosus, and type I diabetes (25, 26, 27). A number of studies have demonstrated that vitD3 modulates the activity of monocytes/macrophages and dendritic cells.
The inhibition of Th1 development by vitD3 is thought to be primarily mediated via its action on the APC as a consequence of reduced IL-12 production after vitD3 treatment (31).
In the present study we demonstrated that vitD3 affects the Th1-Th2 balance in that it inhibits Th1 and augments Th2 cell development.
Changes of vitamin D3 serum concentrations at the onset of immune-mediated type 1 (insulin-dependent) diabetes mellitus
Diabetes Research Institute, Heidelberg, FRG.Several hormones such as 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3), alpha-MSH, or ACTH have been found to interact extensively with the immune system. In view of the immune-mediated nature of Type 1 (insulin-dependent) diabetes mellitus, 49 recently diagnosed diabetic patients were investigated in terms of serum 1,25-(OH)2D3-levels, 25-hydroxyvitamin D3(25-(OH)D3), alpha-MSH and ACTH, and compared with 42 healthy controls. A marked decrease of 1,25-(OH)2D3-levels was found at onset of Type 1 (insulin-dependent) diabetes compared to normal controls (39 +/- 2 vs 55 +/- 4 pg/ml, p less than 0.01). Grouping patients according to season (winter or summer) of diabetes onset and blood sampling, it was demonstrated that the decrease of 1,25-(OH)2D3 was primarily present during summer and due to a loss of the seasonal rhythm of this hormone observed in healthy controls (summer: patients vs controls 41 +/- 2 vs 63 +/- 4 pg/ml, p less than 0.001; winter: 37 +/- 3 vs 33 +/- 3 pg/ml, n.s.). Serum concentrations of 25-(OH)D3 were closely correlated with those of 1,25-(OH)2D3, both in controls (r = 0.55, p less than 0.002) and diabetic patients (r = 0.41, p less than 0.05), yielding a similar loss of seasonal variation also of this vitamin D3 metabolite in Type 1 (insulin-dependent) diabetic patients. No difference was found in the mean and median values of alpha-MSH and ACTH between IDDM patients and controls, although patients exhibited much higher variation of alpha-MSH levels than did controls.