Chimeric specific antigen epitope-carrying dendritic cells induce interleukin-17( ) regulatory T cells to suppress food allergy.
Chimeric specific antigen epitope-carrying dendritic cells induce interleukin-17( ) regulatory T cells to suppress food allergy.
复制标题
携带嵌合特异性抗原表位的树突状细胞诱导白细胞介素17（）调节性T细胞抑制食物过敏。
DOI：
10.1111/cea.13528
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发表时间：
2020
影响因子：
6.1
通讯作者：
Yang Ping-Chang
中科院分区：
文献类型：
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作者：
Xu Ling-Zhi;Xie Rui-Di;Xie Hai;Ju Ji-Yu;Fu Xiao-Yan;Di Da-Lin;Peng Mei-Yu;Gao Wei;Zhang Yuan-Yi;Yu Dian;Liu Jiang-Qi;Yang Gui;Liu Zhi-Qiang;Liu Zhi-Gang;Yang Ping-Chang
本研究旨在构建携带嵌合抗原肽（chimerical antigen，Ag）的树突状细胞（DCs，CAP‐DCs），诱导白细胞介素（IL）-17+诱导型T细胞活化因子（interleukin，IL）-17 + inducible T细胞活化因子（iT细胞活化因子，iT细胞活化，iT细胞CAP是一种融合蛋白，由抗DEC 205抗体的重组scFv片段和卵清蛋白（OVA）表位（IC）组成。结果CAP-DCs的特点是在细胞表面存在scFv-IC复合物，适度表达CD 80和CD 86以及IL-6、IL-23、转化生长因子（TGF）-β和CCR 9。在用CAP-DC被动转移或注射scFv-IC后，在FA小鼠的肠固有层中诱导Ag特异性IL-17+ Foxp 3 + iT细胞。iTclad对Ag特异性Th 2应答显示出免疫抑制作用。CAP-DCs或scFv-IC过继转移FA小鼠，均能显著降低抗原特异性Th 2细胞数量，并以抗原特异性方式抑制FA应答。结论与临床意义CAP-DCs可通过诱导抗原特异性IL-17+ Foxp 3 + iT细胞，抑制抗原特异性Th 2应答，从而改善FA应答。产生CAP-DCs在FA的治疗中具有翻译潜力。
BackgroundThe on‐purpose‐modulated dendritic cells (DCs) have shown charming effects on restoring immune regulatory functions in subjects with immune diseases.ObjectiveThis study aims to construct DCs carrying chimerical antigen (Ag) peptides (CAP‐DCs) to induce interleukin (IL)‐17+ inducible Tregs (iTregs) to alleviate food allergy (FA) in a murine model.MethodsIn this study, we constructed CAP‐DCs. The CAP is a fusion protein, consisting of a segment of recombinant scFv of anti‐DEC205 antibody and an ovalbumin (OVA) epitope (IC). A murine OVA‐FA model was developed to test the effects of CAP‐DCs on suppressing the allergic response in the intestine.ResultsThe CAP‐DCs are characterized as that a complex of scFv‐IC is presented on the surface of the cells, moderately express CD80 and CD86 as well as IL‐6, IL‐23, transforming growth factor (TGF)‐β and CCR9. After being passively transferred with CAP‐DCs or injection of scFv‐IC, Ag‐specific IL‐17+ Foxp3+ iTregs were induced in the intestinal lamina propria of FA mice. The iTregs showed immune suppressive effects on Ag‐specific Th2 response. FA mice were adoptively transferred with the CAP‐DCs or scFv‐IC injection, which resulted in a significant decrease in the number of Ag‐specific Th2 cells and suppression of FA response in an Ag‐specific manner.Conclusions and Clinical RelevanceCAP‐DCs can ameliorate FA response by inducing Ag‐specific IL‐17+ Foxp3+ iTregs and suppressing Ag‐specific Th2 response. To generate CAP‐DCs has the translational potential in the treatment of FA.