James Jamaal, Weaver Veronika, Cantorna Margherita T
Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802.
Molecular Medicine Graduate Program, Pennsylvania State University, University Park, PA 16802; and.
J Immunol. 2017 Feb 1;198(3):1164-1171. doi: 10.4049/jimmunol.1601213. Epub 2016 Dec 21.
Vitamin D deficiency is associated with the development of asthma and allergy. The active form of vitamin D [1,25(OH)D] regulates B cells in vitro and mice without the vitamin D receptor (VDR knockout [KO]) have high serum IgE. Whole-body VDR KO, T cell-specific VDR (T-VDR) KO, B cell-specific VDR (B-VDR) KO, and vitamin D deficient mice were used to determine the targets of vitamin D in the regulation of IgE in vivo. Vitamin D deficient, VDR KO, and B-VDR KO mice developed hyper-IgE, whereas T-VDR KO mice did not. The data show that IL-10 secretion by B cells and CD1d expression on IL-10 secreting B cells was lower in VDR KO mice. Mesenteric lymph node cultures from VDR KO and B-VDR KO mice secreted higher IgE ex vivo than wild-type (WT) cultures, and the addition of IL-10 eliminated the difference in IgE production between VDR KO and WT cultures. The increase in IgE in VDR KO mice was 2-fold greater than in the B-VDR KO mice, suggesting that VDR deficiency in non-B cells contributes to hyper-IgE in vivo. Antibiotic depletion of the microbiota raised serum IgE 4-fold in both WT and VDR KO mice. The VDR directly and indirectly regulates IgE production in B cells. Through the VDR, vitamin D is an environmental factor that helps to maintain low serum IgE responses.
维生素D缺乏与哮喘和过敏的发生有关。维生素D的活性形式[1,25(OH)D]在体外调节B细胞，缺乏维生素D受体的小鼠（维生素D受体基因敲除[KO]）血清IgE水平较高。利用全身维生素D受体基因敲除小鼠、T细胞特异性维生素D受体（T-VDR）基因敲除小鼠、B细胞特异性维生素D受体（B-VDR）基因敲除小鼠和维生素D缺乏小鼠来确定维生素D在体内调节IgE的靶点。维生素D缺乏小鼠、维生素D受体基因敲除小鼠和B-VDR基因敲除小鼠出现高IgE血症，而T-VDR基因敲除小鼠则未出现。数据显示，维生素D受体基因敲除小鼠中B细胞分泌的IL-10以及分泌IL-10的B细胞上的CD1d表达较低。维生素D受体基因敲除小鼠和B-VDR基因敲除小鼠的肠系膜淋巴结培养物在体外分泌的IgE高于野生型（WT）培养物，添加IL-10消除了维生素D受体基因敲除小鼠和野生型培养物之间IgE产生的差异。维生素D受体基因敲除小鼠中IgE的增加比B-VDR基因敲除小鼠大2倍，这表明非B细胞中维生素D受体缺乏导致体内高IgE血症。微生物群的抗生素清除使野生型和维生素D受体基因敲除小鼠的血清IgE升高4倍。维生素D受体直接和间接调节B细胞中IgE的产生。通过维生素D受体，维生素D是一种有助于维持低血清IgE反应的环境因素。
