1α, 25-dihydroxyvitamin D3 suppresses differentiation, maturation and activation of dendritic cells from patients with systemic lupus erythematosus

Abstract

BACKGROUND: Dendritic cells (DC), professional antigen presenting cells, are believed to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). 1α, 25-dihydroxyvitamin D3 (VitD3), in addition to its effect on bone metabolism, has been increasingly recognised to have immunomodulatory effects. OBJECTIVE: To examine the effect of VitD3 on the differentiation, maturation, and activation of DCs in SLE patients. METHODS: CD14+ monocyte–derived DCs from SLE patients and age- and sex-matched controls were derived from growth medium cultured with IL-4, GM-CSF. Mature DCs were induced by addition of lipopolysaccharide and tumour necrosis factor-α in the presence or absence of VitD3 (1×10-10 M) and/or dexamethasone (1×10-6 M). The expression of CD1a, a DC marker and markers of maturation and co-stimulatory molecules such as CD80, CD86, CD40, HLA-DR and CD83 were examined by flow cytometry. After stimulation of DCs with CD40L for 24 hours, the production of pro-inflammatory cytokines including IL-12 and IL-6, were measured by ELISA kits. RESULTS: VitD3 suppresses differentiation of monocytes into DCs as showed by the decreased expression of CD1a (P<0.05). VitD3 inhibits the expression of maturation markers including CD86, CD40 and CD83 (P<0.05), but not CD80 and HLA-DR. This effect was more marked in SLE patients (n=14) than controls (n=9). In combination with dexamethasone, VitD3 displayed more potent immunosuppressive effect on DCs. Under the effect of VitD3, stimulated DCs produced less of IL-12 (3.1 vs 10.4 pg/mL, P=0.02) and IL-6 (216.0 vs 224.0 pg/mL, P=0.21) in SLE patients as well as controls (8.0 vs 36.6 μg/mL, P=0.01 for IL-12) and (380.7 vs 415.2 pg/mL, P=0.04 for IL-6). CONCLUSION: VitD3 is found to inhibit differentiation, maturation, and activation of DCs in vitro in both SLE patients and controls and may be considered as immunomodulatory agent in the treatment of SLE.