Forkhead box protein-3 (Foxp3)-producing dendritic cells suppress allergic response
Forkhead box protein-3 (Foxp3)-producing dendritic cells suppress allergic response
复制标题
产生叉头盒蛋白 3 (Foxp3) 的树突状细胞可抑制过敏反应。
DOI：
10.1111/all.13088
复制
发表时间：
2017-06-01
期刊：
影响因子：
12.4
通讯作者：
Yang, P. -C.
中科院分区：
文献类型：
--
作者：
Liu, X. -Y.;Xu, L. -Z.;Yang, P. -C.
背景：耐受性树突状细胞（DC）的产生尚不完全清楚。叉头盒蛋白-3 （Foxp3）是参与免疫耐受的重要分子。本研究验证了dc表达Foxp3的假设，Foxp3可被葡萄球菌肠毒素B （staphylococcus enterotoxin B， SEB）上调。方法：采用实时RT-PCR、Western blotting、流式细胞术、染色质免疫沉淀法检测DCs中Foxp3的表达。结果：我们观察到0.25 ~ 0.5 μ g/只SEB处理小鼠肠道中产生TGF- β的CD4(+) T细胞和TGF- β生成dc的频率较高，而1 ~ 10 μ g/只SEB处理小鼠肠道中以IL-4(+) CD4(+) T细胞和TIM4(+) dc为主。在培养中用SEB处理DCs诱导tgf - β启动子位点的高水平Foxp3。Foxp3的功能被STAT6（信号传感器和激活因子转录-6）阻断；后者是通过在培养物中以100 ~ 400 ng/ml剂量暴露于SEB诱导的。特异性免疫治疗（SIT）联合SEB治疗过敏小鼠，其治疗效果明显优于单独应用特异性免疫治疗。结论：树突状细胞具有表达Foxp3的能力，并可通过SEB上调Foxp3的表达。
Background: The generation of the tolerogenic dendritic cells (DC) is not fully understood yet. Forkhead box protein-3 (Foxp3) is an important molecule in the immune tolerance. This study tests a hypothesis that DCs express Foxp3, which can be upregulated by Staphylococcal enterotoxin B (SEB).Methods: The expression of Foxp3 by DCs was evaluated by real-time RT-PCR, Western blotting, flow cytometry, and chromatin immunoprecipitation assay.Results: We observed that mice treated with SEB at 0.25-0.5 mu g/mouse showed high frequencies of transforming growth factor (TGF)-beta-producing CD4(+) T cells and TGF-beta-producing DCs in the intestine, while the IL-4(+) CD4(+) T cells and TIM4(+) DCs were dominated in the intestine in mice treated with SEB at 1-10 mu g/mouse. Treating DCs with SEB in the culture induced high levels of Foxp3 at the TGF-beta promoter locus. The function of Foxp3 was blocked by STAT6 (signal transducer and activator transcription-6); the latter was induced by exposing DCs to SEB in the culture at doses of 100-400 ng/ml. Treating allergic mice with specific immunotherapy (SIT) together with SEB significantly promoted the therapeutic effects on the allergic responses than treating with SIT alone.Conclusion: Dendritic cells have the capacity to express Foxp3, which can be upregulated by exposure to SEB.