Abstract：
Th17/Treg cell balance is essential for immune homeostasis and when disrupted, is associated with the occurrence and development of inflammation in numerous autoimmune diseases. However, its contribution in pathophysiology of uveitis remains unexplored. In this study, we deciphered the role of Th17/Treg cell balance in autoimmune uveitis subjects. Using flow cytometry, we detected the frequencies and absolute count of both Th17 and Treg cells in the aqueous humor and peripheral blood of patients and healthy controls. Our results for the first time reveal a significant increase (p < 0.01 and p < 0.005) in Th17 population alongside a significant decrease (p < 0.001 and p < 0.003) in Treg cell population in both the aqueous humor and PBMCs of uveitis patients. Further we analyzed the expression of Th17-Treg associated genes and cytokines via qPCR and ELISA respectively. These findings align with our flow cytometry results, as evident by a significant (p < 0.002) up-regulation of IL-17 and a concurrent down regulation of IL-10 at transcriptional levels. Moreover, IL-17A cytokine was found to be substantially high (p < 0.001) and IL-10 (p < 0.02) down regulated in serum. Interestingly, we demonstrated a significant correlation of Th17/Treg cells in aqueous humor with those in peripheral blood. Conclusively, our results suggest the pivotal role of Th17/Treg cell axis in the immuno-pathophysiology of human uveitis. Further we propose the therapeutic potential of targeting this novel axis for ameliorating the disease burden associated with uveitis.
摘要：
Th17/Treg细胞平衡对于免疫稳态至关重要，当被破坏时，炎症与多种自身免疫性疾病的发生发展有关。然而,其在葡萄膜炎病理生理学中的贡献仍未被探索。在这项研究中,我们破译了Th17/Treg细胞平衡在自身免疫性葡萄膜炎中的作用。使用流式细胞术，我们检测了患者和健康对照组的房水和外周血中Th17和Treg细胞的频率和绝对计数。我们的结果首次揭示了Th17群体的显着增加（p<0.01和p<0.005），同时葡萄膜炎患者的房水和PBMC中Treg细胞群体的显着减少（p<0.001和p<0.003）。进一步我们分别通过qPCR和ELISA分析了Th17-Treg相关基因和细胞因子的表达。这些发现与我们的流式细胞术结果一致，如IL-17的显著上调(p<0.002)和IL-10在转录水平的同时下调所证明的。此外，发现IL-17A细胞因子在血清中显著高(p<0.001)并且IL-10(p<0.02)下调。有趣的是,我们证明了房水中Th17/Treg细胞与外周血中Th17/Treg细胞的显着相关性。最后，我们的结果提示Th17/Treg细胞轴在人类葡萄膜炎的免疫病理生理学中的关键作用.此外，我们提出了靶向该新轴以改善与葡萄膜炎相关的疾病负担的治疗潜力。
