Vitamin D3 is necessary for human dendritic cells to respond to bacterial products

Abstract Background: Differentiated DCs are matured in the presence of lipopolysaccharide, a product of gram-negative bacteria. We hypothesized that additional bacterial products are able to cause DC maturation and that 1,25-dihydroxyvitamin D3 is capable of regulating this process by controlling cytokine secretion. Methods: DCs were differentiated and matured from human monocytes in the presence or absence of vitD3. DC maturation was induced by lipopolysaccharide and peptidoglycan. DC differentiation and maturation were monitored by morphology change and expression of surface molecules. Cytokine secretion of IL-6, IL-8, IL-10, and IL-12p70 was measured by ELISA. Expression of vitD3 receptor in DCs was determined by Western blotting. Results: The presence of vitD3 inhibited LPS-induced DC maturation, including formation of dendrites on DCs consistent with the phenotype of immature DCs. VitD3 was necessary for LPS- and PGN-induced secretion of IL-6, IL-8 and IL-10, whereas vitD3 inhibited LPS-induced secretion of IL-12. Furthermore, both LPS and PGN could act in synergy with vitD3 to increase the expression of the vitD3 receptor in DC. Conclusions: The presence of vitD3 was necessary for LPS- and PGN-induced secretion of IL-6, IL-8 and IL-10 in DCs. The expression of vitD3 receptor in LPS- or PGN-matured DC was enhanced in a synergy with vitD3. Elucidating the mechanisms behind this may be of importance for understanding the role of vitD3 during induction of peripheral tolerance.