Liu Lan, Xu Yongfeng, Wang Jianyong, Li Huiyan
Department of Ophthalmology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P.R. China.
Mol Vis. 2009 Dec 31;15:2938-44.
Interleukin (IL)-21 has recently been shown to play a vital role in the development of many autoimmune diseases. Our study is designed to investigate the alteration and possible function of IL-21 in the development of an experimental autoimmune uveitis (EAU) model.
EAU was induced in B10.RIII mice by subcutaneous injection of interphotoreceptor retinoid-binding protein (IRBP) 161-180 emulsified with complete Freund's adjuvant (CFA) and evaluated by clinical and histopathologic observation. IL-21 and IL-21R mRNA expressions in cells of draining lymph node (DLN) and spleen in EAU and control mice were determined by reverse transcription-PCR. The frequencies of interleukin-21 receptor positive cells were also examined using flow cytometry. IL-17 levels in the supernatant of the cell culture upon IL-21 stimulation were assayed by enzyme-linked immunosorbent assay.
Results showed that EAU was successfully induced by IRBP161-180. Expression of IL-21 mRNA was significantly increased in cells of DLN and spleen in EAU compared with recovery phase mice and normal controls. IL-21R was also found upregulated in DLN and spleen cells of EAU mice by reverse transcription-PCR and flow cytometry. Cells in EAU cultured with IL-21 combined with transforming growth factor-beta induced increased production of IL-17.
The findings revealed that increased IL-21 and IL-21R expression may be involved in the development of EAU, possibly by promoting IL-17 secretion.
白细胞介素(IL)-21最近被证明在多种自身免疫性疾病的发展中起关键作用。我们的研究旨在探讨IL-21在实验性自身免疫性葡萄膜炎(EAU)模型发展过程中的变化及其可能的功能。
通过皮下注射与完全弗氏佐剂(CFA)乳化的光感受器间维生素A结合蛋白(IRBP)161-180诱导B10.RIII小鼠发生EAU,并通过临床和组织病理学观察进行评估。采用逆转录聚合酶链反应(RT-PCR)测定EAU小鼠和对照小鼠引流淋巴结(DLN)及脾脏细胞中IL-21和IL-21R mRNA的表达。还使用流式细胞术检测白细胞介素-21受体阳性细胞的频率。通过酶联免疫吸附测定法检测IL-21刺激后细胞培养上清液中的IL-17水平。
结果显示IRBP161-180成功诱导了EAU。与恢复期小鼠和正常对照相比,EAU小鼠DLN和脾脏细胞中IL-21 mRNA的表达显著增加。通过RT-PCR和流式细胞术还发现EAU小鼠的DLN和脾脏细胞中IL-21R上调。用IL-21联合转化生长因子-β培养的EAU细胞诱导IL-17产生增加。
研究结果表明,IL-21和IL-21R表达增加可能参与了EAU的发展,可能是通过促进IL-17的分泌。