IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease
IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease
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在 Vogt-Koyanagi-Harada 病中，IL-23 促进 CD4 T 细胞产生 IL-17。
DOI：
10.1016/j.jaci.2007.01.010
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发表时间：
2007-05-01
影响因子：
14.2
通讯作者：
Kijlstra, Aize
中科院分区：
文献类型：
--
作者：
Chi, Wei;Yang, Peizeng;Kijlstra, Aize
背景：Vogt-Koyanagi-Harada（VKH）病是一种全身性难治性自身免疫性疾病。IL-23通过诱导产生IL-17的CD 4（+）T细胞在自身免疫性疾病中发挥重要作用，目的：探讨VKH病患者外周血IL-23和IL-17的表达及IL-23对IL-17产生的影响。分别采用RT-PCR和ELISA法检测外周血单个核细胞（PBMC）中IL-23 p19 mRNA和IL-23蛋白的表达。通过ELISA测定在不存在或存在重组（r）IL-23、rIL-12或抗IFN-γ的情况下培养的PBMC和CD 4（+）T细胞的上清液中的IL-17水平。活动性葡萄膜炎患者PBMC中IL-23 p19 mRNA水平升高，血清和PBMC上清液中IL-23水平升高，以及通过多克隆刺激的PBMC和CD 4 + T细胞增加IL-17的产生。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rIL-23存在下，活动性葡萄膜炎患者的IL-17产生显著增加。rIL-23和rIL-12均能增强IFN-γ的产生。结论：IL-23刺激CD 4 + T细胞产生IL-17可能是VKH病患者葡萄膜炎发生的原因。
Background: 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.Objective: 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.Methods: 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.Results: 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.Conclusion: 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.Clinical implications: This study provides a new insight into the mechanism involved in the development of VKH disease.