Coordinated gene expression of Th17- and Treg-associated molecules correlated with resolution of the monophasic experimental autoimmune uveitis
Coordinated gene expression of Th17- and Treg-associated molecules correlated with resolution of the monophasic experimental autoimmune uveitis
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发表时间：
2011-06
期刊：
影响因子：
2.2
通讯作者：
Xiuzhi Jia;Minghui Hu;Caihong Wang;Chunyu Wang;Fengyun Zhang;Qinglian Han;R. Zhao;Qi Huang;Hongwei Xu;Huiping Yuan;H. Ren
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作者：
Xiuzhi Jia;Minghui Hu;Caihong Wang;Chunyu Wang;Fengyun Zhang;Qinglian Han;R. Zhao;Qi Huang;Hongwei Xu;Huiping Yuan;H. Ren
目的探讨T细胞介导的免疫反应在单相实验性自身免疫性葡萄膜炎(EAU)中的作用。方法用光感受器间类视黄酸结合蛋白多肽免疫Lewis大鼠，诱导单相EAU。用优化的实时定量RT-PCR法连续检测Th17相关分子的相对表达，包括白介素6(IL-6)、转化生长因子-β(转化生长因子-β)、白介素23p19(IL-23p19)、白介素23p40(IL-23p40)、CD4、CD8、主要组织相容性复合体I(MHC I)、主要组织相容性复合体II(MHC II)、白介素17(IL-17)、白介素17F(IL-17F)、白介素17受体A(IL-17RA)、维甲酸相关孤儿受体γ(RORγt)和趋化因子受体6(CCR6)。除了Treg相关的叉头盒P3(Foxp3)、C-X-C趋化因子受体5(CXCR5)和分化簇25(CD25)外，还在EAU的起始期、效应期和解决期进行了表达，并与对照组动物免疫后14天的表达进行了比较。免疫组织化学方法检测视网膜IL-17的表达。荧光显微镜动态分析胶质纤维酸性蛋白视网膜星形胶质细胞、神经元III型β-微管蛋白(Tuj1+)视网膜神经节细胞和CD11b+小胶质细胞。结果通过多种T细胞相关因子在mRNA水平的相对表达，我们的结果表明T细胞活性良好，与自身免疫性炎症的启动同步，随后单相性EAU的消退。免疫平衡是通过Th17和Treg相关因子的协同表达实现的。这些因子的表达模式和IL-17抗体的免疫化学结果表明，浸润性免疫细胞和常驻神经细胞之间可能存在强烈的串扰，在疾病过程中显著激活。结论T细胞介导的免疫反应在单相性EAU的消退中发挥了积极作用。
Purpose To investigate the role of T-cell-mediated immune response in a monophasic experimental autoimmune uveitis (EAU). Methods A monophasic EAU was induced in Lewis rats by immunization with interphotoreceptor retinoid-binding protein peptide. Optimized quantitative real-time RT–PCR was used for consecutive measurement of the relative expression of Th17-associated molecules, including interleukin 6 (IL-6), transforming growth factor-β (TGF-β), interleukin 23p19 (IL-23p19), interleukin 23p40 (IL-23p40), CD4, CD8, major histocompatibility complex I (MHC I), major histocompatibility complex II (MHC II), interleukin 17 (IL-17), interleukin 17F (IL-17F), interleukin 17 receptor A (IL-17RA), retinoic acid-related orphan receptor γt (RORγt) and Chemokine receptor 6 (CCR6), in addition to Treg-related forkhead box P3 (Foxp3), C-X-C chemokine receptor type 5 (CXCR5), and cluster of differentiation 25 (CD25) at the initiation, effector, and resolution phases of EAU and compared with those at 14 days post-immunization of control animals. Immunohistochemisty was used to examine IL-17 expression in retinas. Glial fibrillary acidic protein retinal astrocytes, Neuronal class III β-Tubulin(Tuj1+)retinal ganglion cells, and infiltrating CD11b+ microglia were analyzed by fluorescent microscopy in a kinetic manner. Results Our results indicated well organized T-cell activity, measured by relative expression of multiple T-cell-related factors at the mRNA level, synchronized with the initiation of autoimmune inflammation, and thereafter resolution of the monophasic EAU. Immune balance was achieved several times through coordinated expression of Th17- and Treg-related factors. The expression pattern of these factors and results from immunochemistry with an IL-17 antibody indicated that there may be intensive crosstalk between infiltrating immune cells and the resident neural cells, which were significantly activated during the course of disease. Conclusions T-cell-mediated immune response played a positive role in resolution of the monophasic EAU.