1,25-dihydroxYvitamin D3 promotes IL-10 production in human B cells

1,25-dihydroxyvitamin D-3 (calcitriol) regulates immune responses, e.g., inhibits expression of IgE by B cells and enhances expression of IL-10 by dendritic cells and T cells. We report here that activation of human B cells by B cell receptor, CD40 and IL-4 signals induces expression of the gene for 25-hydroxyvitamin-D3-l alpha-hydroxylase (CYP1 alpha). Accordingly, these B cells generate and secrete significant amounts of calcitriol. in activated B cells calcitriol induces expression of the genes Cyp24, encoding a vitamin D hydroxylase, and Trpu6, encoding a calcium selective channel protein. Calcitriol enhances IL-10 expression of activated B cells more than threefold, both by recruiting the vitamin D receptor to the promoter of 11-10, and to lesser extent by modulation of calcium-dependent signaling. The molecular link in activated B cells between vitamin D signaling, expression of IgE and Il-10, and their ability to produce calcitriol from its precursor, suggest that pro-vitamin D (25-hydroxyvitamin D-3) can be used as a modulator of allergic immune responses.