Yang Gui, Geng Xiao-Rui, Liu Zhi-Qiang, Liu Jiang-Qi, Liu Xiao-Yu, Xu Ling-Zhi, Zhang Huan-Ping, Sun Ying-Xue, Liu Zhi-Gang, Yang Ping-Chang
From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China, the Brain Body Institute, McMaster University, Hamilton, Ontario L8N 4A6, Canada, and Longgang Central Hospital, Shenzhen 518116, China.
From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China.
J Biol Chem. 2015 May 15;290(20):12858-67. doi: 10.1074/jbc.M114.623421. Epub 2015 Apr 3.
Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. In this study, a B cell-deficient mouse model was created by injecting an anti-CD20 antibody. The frequency of tolerogenic dendritic cell (TolDC) was assessed by flow cytometry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The expression of thrombospondin-1 (TSP1) was assessed by quantitative real-time RT-PCR, Western blotting, and methylation-specific PCR. The results showed that B cells were required in the generation of the TGF-β-producing TolDCs in mice. B cell-derived TSP1 converted the latent TGF-β to the active TGF-β in DCs, which generated TGF-β-producing TolDCs. Exposure to IL-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. In conclusion, B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy.
在过敏环境中恢复抗原（Ag）特异性免疫耐受是难治的。B细胞参与免疫调节。B细胞是否促进过敏环境中Ag特异性免疫耐受的产生尚需进一步研究。本文旨在阐明B细胞在过敏环境中恢复Ag特异性免疫耐受的机制。在本研究中，通过注射抗CD20抗体建立了B细胞缺陷小鼠模型。通过流式细胞术评估耐受性树突状细胞（TolDC）的频率。通过酶联免疫吸附测定法测定细胞因子水平。通过定量实时RT-PCR、蛋白质印迹和甲基化特异性PCR评估血小板反应蛋白-1（TSP1）的表达。结果表明，小鼠中产生分泌TGF-β的TolDC需要B细胞。B细胞来源的TSP1将DCs中潜伏的TGF-β转化为活性TGF-β，从而产生分泌TGF-β的TolDC。暴露于IL-13通过增强TSP1基因DNA甲基化抑制B细胞中TSP1的表达。用Ag特异性免疫疗法和IL-13拮抗剂治疗食物过敏小鼠可恢复TolDC的产生并增强特异性免疫疗法的效果。总之，B细胞在过敏环境中特异性免疫耐受的恢复中起关键作用。在过敏环境中阻断IL-13促进了TolDC的产生并增强了免疫疗法的治疗效果。
