Immunopathogenic roles for both Th1 (CD4⁺IFN‐γ⁺) and Th17 (CD4⁺IL‐17A⁺) cells have been demonstrated in experimental autoimmune uveitis (EAU). However, the role for Th17/Th1 (CD4⁺ T cells co‐expressing IFN‐γ and IL‐17A) cells in EAU is not yet understood. Using interphotoreceptor retinoid‐binding protein peptide‐induced EAU in mice, we found increased levels of Th17/Th1 cells in EAU retinae (mean 9.6 ± 4.2%) and draining LNs (mean 8.4 ± 3.9%; p = 0.01) relative to controls. Topical dexamethasone treatment effectively reduced EAU severity and decreased retinal Th1 cells (p = 0.01), but had no impact on retinal Th17/Th1 or Th17 cells compared to saline controls. Using in vitro migration assays with mouse CNS endothelium, we demonstrated that Th17/Th1 cells were significantly increased within the migrated population relative to controls (mean 15.6 ± 9.5% vs. 1.9 ± 1.5%; p = 0.01). Chemokine receptor profiles of Th17/Th1 cells (CXCR3 and CCR6) did not change throughout the transendothelial migration process and were unaffected by dexamethasone treatment. These findings support a role for Th17/Th1 cells in EAU and their resistance to steroid inhibition suggests the importance of targeting both Th17 and Th17/Th1 cells for improving therapy.

中文翻译：

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实验性自身免疫性葡萄膜炎中功能不同的IFN-γ+ IL-17A + Th细胞：T细胞异质性，迁移和类固醇反应。

Th1（CD4 ⁺ IFN-γ ⁺）和Th17（CD4 ⁺ IL-17A ⁺）细胞的免疫致病作用已在实验性自身免疫性葡萄膜炎（EAU）中得到证实。但是，尚未了解在EAU中Th17 / Th1（CD4 ⁺ T细胞共表达IFN-γ和IL-17A）细胞的作用。使用光感受器类视黄醇结合蛋白肽诱导的小鼠EAU，我们发现EAU视网膜中Th17 / Th1细胞水平升高（平均9.6±4.2％），引流性LN升高（平均8.4±3.9％; p  = 0.01）。局部地塞米松治疗可有效降低EAU严重程度并减少视网膜Th1细胞（p = 0.01），但与盐水对照组相比，对视网膜Th17 / Th1或Th17细胞没有影响。使用小鼠中枢神经系统内皮细胞的体外迁移分析，我们证明相对于对照，Th17 / Th1细胞在迁移的群体中显着增加（平均值为15.6±9.5％对1.9±1.5％；p  = 0.01）。Th17 / Th1细胞（CXCR3和CCR6）的趋化因子受体谱在整个跨内皮迁移过程中没有改变，并且不受地塞米松治疗的影响。这些发现支持Th17 / Th1细胞在EAU中的作用，并且它们对类固醇抑制的抗性提示了同时靶向Th17和Th17 / Th1细胞以改善治疗的重要性。