RESUMEN
Human dendritic cells (DC) can be differentiated from blood monocytes in the presence of GM-CSF and IL-4 and matured by lipopolysaccharide (LPS). Vitamin D3 inhibits the maturation of human DC measured by changes in surface expression of HLA-DR, CD14, CD40, CD80, CD83, and CD86. We here examine the function of vitamin D3 during DC maturation. One of the earliest changes to LPS-induced maturation was an increase in CD83 expression. Vitamin D3 inhibited the increase in expression of HLA-DR, CD40, CD80, CD83, and CD86 and the decrease in expression of CD14, which was paralleled morphologically by vitamin D3-induced inhibition of dendritic cell differentiation. Vitamin D3 acted in synergy with the TLR agonists LPS and peptidoglycan (PGN) in inducing IL-6, IL-8, and IL-10, whereas vitamin D3 completely inhibited LPS-induced secretion of IL-12. The synergy occurred at concentrations where neither vitamin D3 nor the TLR agonists alone induced measurable cytokine secretion. Both LPS and PGN enhanced the level of the vitamin D3 receptor (VDR). Taken together, these data demonstrated that vitamin D3 and TLR agonists acted in synergy to alter secretion of cytokines from human DC in a direction that may provide an anti-inflammatory environment.
Asunto(s)
Colecalciferol/farmacología , Células Dendríticas/efectos de los fármacos , Lipopolisacáridos/farmacología , Peptidoglicano/farmacología , Receptores Toll-Like/agonistas , Antígenos CD/genética , Antígenos CD/inmunología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Células Dendríticas/citología , Células Dendríticas/inmunología , Sinergismo Farmacológico , Regulación de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Antígenos HLA-DR/genética , Antígenos HLA-DR/inmunología , Humanos , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Receptores de Calcitriol/genética , Receptores de Calcitriol/inmunología , Receptores Toll-Like/genética , Receptores Toll-Like/inmunologíaRESUMEN
A perturbed immunoregulation may be part of the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). In this study, we demonstrate a dichotomy within the frequency of Treg among newly diagnosed RRMS patients but not in healthy controls. A group of RRMS patients was characterized by a significantly lower percentage of Treg cells than that of their matched, healthy controls, and this was inversely correlated with their score on the expanded disability status scale (EDSS). Since the EDSS reflected severity of the last attack, this study demonstrates a correlation between low frequency of Treg and severity of clinical disease in RRMS.