Chi Wei, Yang Peizeng, Li Bing, Wu Changyou, Jin Haoli, Zhu Xuefei, Chen Lina, Zhou Hongyan, Huang Xiangkun, Kijlstra Aize
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University, Guanzhou, China.
J Allergy Clin Immunol. 2007 May;119(5):1218-24. doi: 10.1016/j.jaci.2007.01.010. Epub 2007 Mar 1.
Vogt-Koyanagi-Harada (VKH) disease is a systemic refractory autoimmune disease. IL-23 has been thought to play a critical role in autoimmune disease through inducing the development of IL-17-producing CD4(+) T cells.
To investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in patients with VKH disease.
Blood samples were taken from 25 patients with VKH disease and 16 healthy controls. Peripheral blood mononuclear cells (PBMCs) were subjected to analysis of IL-23p19 mRNA and IL-23 protein expression using RT-PCR and ELISA, respectively. The IL-17 levels in the supernatants of PBMCs and CD4(+) T cells cultured in the absence or presence of recombinant (r)IL-23, rIL-12, or anti-IFN-gamma were determined by ELISA.
The patients with VKH disease with active uveitis showed an elevated level of IL-23p19 mRNA in PBMCs, higher IL-23 in the serum and supernatants of PBMCs, and increased production of IL-17 by polyclonally stimulated PBMCs and CD4(+) T cells. Recombinant IL-23 significantly enhanced IL-17 production, whereas rIL-12 and IFN-gamma inhibited IL-17 production. More importantly, IL-17 production was significantly increased in patients with active uveitis in the presence of rIL-23. Both rIL-23 and rIL-12 enhanced IFN-gamma production.
The results suggest that IL-23-stimulated production of IL-17 by CD4(+) T cells may be responsible for the development of uveitis seen in patients with VKH disease.
This study provides a new insight into the mechanism involved in the development of VKH disease.
伏格特-小柳-原田（VKH）病是一种全身性难治性自身免疫性疾病。白细胞介素-23（IL-23）被认为通过诱导产生白细胞介素-17的CD4(+) T细胞的发育在自身免疫性疾病中起关键作用。
研究VKH病患者中IL-23和IL-17的表达以及IL-23对IL-17产生的影响。
采集25例VKH病患者和16名健康对照者的血样。分别采用逆转录-聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）对外周血单个核细胞（PBMC）进行IL-23p19 mRNA和IL-23蛋白表达分析。通过ELISA测定在不存在或存在重组（r）IL-23、rIL-12或抗干扰素-γ（IFN-γ）的情况下培养的PBMC和CD4(+) T细胞上清液中的IL-17水平。
患有活动性葡萄膜炎的VKH病患者PBMC中IL-23p19 mRNA水平升高，血清和PBMC上清液中IL-23水平更高，多克隆刺激的PBMC和CD4(+) T细胞产生的IL-17增加。重组IL-23显著增强IL-17的产生，而rIL-12和IFN-γ抑制IL-17的产生。更重要的是，在存在rIL-23的情况下，活动性葡萄膜炎患者的IL-17产生显著增加。rIL-23和rIL-12均增强IFN-γ的产生。
结果表明，IL-23刺激CD4(+) T细胞产生IL-17可能是VKH病患者葡萄膜炎发生的原因。
本研究为VKH病发生机制提供了新的见解。
Zotero 插件