| Autor: |
Bagnoud M; Department of Neurology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.; Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland., Remlinger J; Department of Neurology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.; Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland., Massy M; Department of Neurology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.; Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland., Lodygin D; Institute for Neuroimmunology and Multiple Sclerosis Research, University Medical Center Göttingen, 37075 Göttingen, Germany., Salmen A; Department of Neurology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.; Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland., Chan A; Department of Neurology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.; Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland., Lühder F; Institute for Neuroimmunology and Multiple Sclerosis Research, University Medical Center Göttingen, 37075 Göttingen, Germany., Hoepner R; Department of Neurology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.; Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland. |
| Abstrakt: |
Our previous work demonstrated that vitamin D (VitD) reduces experimental autoimmune encephalomyelitis (EAE) disease severity in wild-type (WT) but not in T cell-specific glucocorticoid (GC) receptor (GR)-deficient (GR lck ) mice. This study aimed to investigate the interplay between the GR- and VitD receptor (VDR) signaling. In vivo, we confirmed the involvement of the GR in the VitD-induced effects in EAE using WT and GR lck mice. Furthermore, we observed that VitD-enhanced T cell apoptosis and T regulatory cell differentiation are diminished in vitro in CD3+ T cells of GR lck but not WT mice. Mechanistically, VitD does not appear to signal directly via the GR, as it does not bind to the GR, does not induce its nuclear translocation, and does not modulate the expression of two GR-induced genes. However, we observed that VitD enhances VDR protein expression in CD3+ T cells from WT but not GR lck mice in vitro, that the GR and the VDR spatially co-localize after VitD treatment, and that VitD does not modulate the expression of two VDR-induced genes in the absence of the GR. Our data suggest that a functional GR, specifically in T cells, is required for the VDR to signal appropriately to mediate the therapeutic effects of VitD. |
