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1,25-dihydroxyvitamin D(3) promotes IL-10 production in human B cells Heine G; Niesner U; Chang HD; Steinmeyer A; Zugel U; Zuberbier T; Radbruch A; Worm MEur J Immunol 2008[Aug]; 38 (8): 2210-81,25-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-D3-1alpha-hydroxylase (CYP1alpha). 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 Trpv6, 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 Il-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.|B-Lymphocytes/*drug effects/metabolism[MESH]|CD40 Antigens/physiology[MESH]|Calcitriol/biosynthesis/*pharmacology[MESH]|Calcium/metabolism[MESH]|Cells, Cultured[MESH]|Humans[MESH]|Interleukin-10/*biosynthesis/genetics[MESH]|Interleukin-4/pharmacology[MESH]|Receptors, Calcitriol/physiology[MESH]|Steroid Hydroxylases/genetics[MESH]|Vitamin D3 24-Hydroxylase[MESH] |
