Decreased sensitivity to 1,25-dihydroxyvitamin D3 in T cells from the rheumatoid joint.

Decreased sensitivity to 1,25-dihydroxyvitamin D3 in T cells from the rheumatoid joint. J Autoimmun. 2017 Oct 21;: Authors: Jeffery LE, Henley P, Marium N, Filer A, Sansom DM, Hewison M, Raza K Abstract 1,25-dihydroxyvitaminD3 (1,25(OH)2D3), has potent anti-inflammatory effects, including suppression of IL-17 + and IFNγ+ T cells implicated in rheumatoid arthritis (RA), but efficacy at the site of active disease is unclear. To investigate this, T cells from synovial fluid (SF) and paired blood of patients with active RA were studied. 1,25(OH)2D3 had significantly less suppressive effect on Th17 cells (IL-17+IFNγ-) and Th17.1 cells (IL-17+IFNγ+) from SF compared to those from blood, and had no effect on SF CD4(+) or CD8(+) IFNγ+ T cell frequencies. Memory T cells (CD45RO+) predominate in SF, and 1,25(OH)2D3 had less effect on memory T cells relative to naïve (CD45RA+) T cells. RT-PCR and flow cytometry showed that this was not due to decreased expression of the vitamin D receptor or its transcription partners in memory T cells. Further studies using stimulated CD4(+) T cells sorted according to IL-17 and IFNγ expression confirmed the ability of 1,25(OH)2D3 to suppress pre-existing cytokines. However, 1,25(OH)2D3 was most effective at suppressing de novo IL-17 and IFNγ induction. Correspondingly, T cell responses to 1,25(OH)2D3 correlated directly with capacity for phenotype change, which was lower in cells from SF compared t...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research