1,25-dihydroxyvitamin D(3) 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-D3-1alpha-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.
Heine
Guido
G
Allergy-Center-Charité, CCM, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Niesner
Uwe
U
Chang
Hyun-Dong
HD
Steinmeyer
Andreas
A
Zügel
Ulrich
U
Zuberbier
Torsten
T
Radbruch
Andreas
A
Worm
Margitta
M
D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D019013:CD40 Antigens / Q000502:physiology; D002117:Calcitriol / Q000096:biosynthesis / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology; D018167:Receptors, Calcitriol / Q000502:physiology; D013250:Steroid Hydroxylases / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase
D019013:CD40 Antigens; D018167:Receptors, Calcitriol; D016753:Interleukin-10; D015847:Interleukin-4; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D002118:Calcium