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雷帕霉素抑制 Th2 驱动的实验性变应性结膜炎。

Rapamycin attenuates Th2-driven experimental allergic conjunctivitis.

机构信息

Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Institute for Visual Science, The Catholic University of Korea, College of Medicine, Seoul, Republic of Korea.

Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon, Kyeonggi-do, Republic of Korea.

出版信息

Clin Immunol. 2018 May;190:1-10. doi: 10.1016/j.clim.2018.02.004. Epub 2018 Feb 9.

Abstract

Allergic conjunctivitis is mediated by eosinophilic infiltration and Th2 type immune responses. This study aims to elucidate the role of rapamycin, mTOR inhibitor, on OVA-induced experimental allergic conjunctivitis (EAC). Rapamycin administration intraperitoneally markedly reduced clinical signs, total and OVA-specific IgE and IgG1/G2a ratio in serum, and conjunctival eosinophilic infiltration. Infiltrations of CD11c dendritic cells and CD4 T cells, and the expressions of chemokines and adhesion molecules in the conjunctiva were attenuated in rapamycin-treated mice, as well as decreased Th1 and Th2 cytokines in the cervical lymph nodes compared to non-treated mice. The expression of mTOR signaling proteins was increased in EAC and reduced by rapamycin treatment. Topical application of rapamycin was also proved to show reduced clinical signs, eosinophil infiltration, and Th2 type immune responses comparable to those from intraperitoneal injection of rapamycin. These findings suggest the therapeutic implications of rapamycin in the attenuation of allergic conjunctivitis.

摘要

变应性结膜炎是由嗜酸性粒细胞浸润和 Th2 型免疫反应介导的。本研究旨在阐明雷帕霉素(mTOR 抑制剂)在卵清蛋白(OVA)诱导的实验性变应性结膜炎(EAC)中的作用。雷帕霉素腹腔注射给药可显著减轻临床症状、血清总 IgE 和 OVA 特异性 IgE 及 IgG1/G2a 比值,以及结膜嗜酸性粒细胞浸润。与未治疗的小鼠相比,雷帕霉素治疗的小鼠结膜中 CD11c 树突状细胞和 CD4 T 细胞浸润以及趋化因子和黏附分子的表达减少,颈淋巴结中 Th1 和 Th2 细胞因子也减少。EAC 中 mTOR 信号蛋白的表达增加,而雷帕霉素治疗则使其减少。与腹腔注射雷帕霉素相比,局部应用雷帕霉素也可显示出减轻临床症状、嗜酸性粒细胞浸润和 Th2 型免疫反应的作用。这些发现提示雷帕霉素可能具有治疗变应性结膜炎的作用。

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