Abstract

Abstract 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‐D3–1α‐hydroxylase (CYP1α). 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. Supporting Information for this article is available at http://www.wiley‐vch.de/contents/jc_2040/2008/38216_s.pdf