Wang Yeqin, Yamamoto Yoshinari, Shigemori Suguru, Watanabe Takafumi, Oshiro Kazushi, Wang Xinyu, Wang Pengfei, Sato Takashi, Yonekura Shinichi, Tanaka Sachi, Kitazawa Haruki, Shimosato Takeshi
Interdisciplinary Graduate School of Science and Technology, Shinshu University, Kamiina, Japan.
Graduate School of Agriculture, Shinshu University, Kamiina, Japan.
Mol Ther. 2015 Feb;23(2):297-309. doi: 10.1038/mt.2014.239. Epub 2014 Dec 15.
Here, we report a simple and low-cost oral oligodeoxynucleotide (ODN) delivery system targeted to the gut Peyer's patches (PPs). This system requires only Dulbecco's modified eagle's medium, calcium chloride, ODNs, and basic laboratory equipment. ODN nanocapsules (ODNcaps) were directly delivered to the PPs through oral administration and were taken up by macrophages in the PPs, where they induced an immune response. Long-term continuous oral dosing with inhibitory/suppressive ODNcaps (iODNcaps, "iSG3caps" in this study) was evaluated using an atopic dermatitis mouse model to visually monitor disease course. Administration of iSG3caps improved skin lesions and decreased epidermal thickness. Underlying this effect is the ability of iSG3 to bind to and prevent phosphorylation of signal transducer and activator of transcription 6, thereby blocking the interleukin-4 signaling cascade mediated by binding of allergens to type 2 helper T cells. The results of our iSG3cap oral delivery experiments suggest that iSG3 may be useful for treating allergic diseases.
在此,我们报告了一种针对肠道派尔集合淋巴结(PPs)的简单且低成本的口服寡脱氧核苷酸(ODN)递送系统。该系统仅需杜氏改良 Eagle 培养基、氯化钙、ODN 和基本的实验室设备。ODN 纳米胶囊(ODNcaps)通过口服直接递送至 PPs,并被 PPs 中的巨噬细胞摄取,在那里它们诱导免疫反应。使用特应性皮炎小鼠模型评估了长期连续口服抑制性/抑制性 ODNcaps(本研究中为“iODNcaps”,即“iSG3caps”)以直观监测疾病进程。给予 iSG3caps 可改善皮肤病变并减小表皮厚度。这种作用的潜在机制是 iSG3 能够结合并阻止信号转导和转录激活因子 6 的磷酸化,从而阻断由过敏原与 2 型辅助性 T 细胞结合介导的白细胞介素 -4 信号级联反应。我们的 iSG3cap 口服递送实验结果表明,iSG3 可能对治疗过敏性疾病有用。