The present study aimed to investigate the relationship between the disturbed balance of CD4+/CD8+, Th17/Treg and the activation of the Notch signaling pathway in experimental autoimmune uveitis (EAU).
Methods
An EAU rat model was induced in Lewis rats, and pathology analysis was performed by hematoxylin and eosin (H&E) staining. CD4+, CD8+, Th17, and Treg levels in spleen, lymph nodes and eye tissues were determined by flow cytometry. Meanwhile, the expression of Notch1, DLL4, IL-10, and IL-17 was determined by quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the inhibitory effect of N-(N-(3,5-difluorophenacetyl-l-alanyl))-S-phenylglycine t-butyl ester (DAPT) on Th17 differentiation by Notch signaling in vitro was further investigated using T lymphocytes from EAU rats on day 12 post-immunization by flow cytometry.
Results
The pathological results showed that inflammatory cell infiltration occurred in ocular tissues in EAU rats. The CD4+/CD8+ and Th17/Treg ratios in EAU rats were apparently higher than those in normal control individuals. Q-PCR and ELISA analyses indicated the expression of Notch1, DLL4, IL-10, and IL-17 in EAU rats gradually increased on day 6 after immunization, peaked on day 12, and then gradually decreased. The dynamic trends in Notch1 and DLL4 expression in EAU rats were identical to those of CD4+/CD8+ and Th17/Treg levels. DAPT can significantly inhibit the activation of Notch signaling, decrease Th17 cell differentiation, and attenuate the level of the Th17 cell lineage, contributing to the balance of the Th17/Treg ratio.
Conclusion
The activation of the Notch signaling pathway can regulate Th17 and Treg cell differentiation, disrupt the CD4+/CD8+ and Th17/Treg balance, and aggravate the severity of EAU; inactivation of the Notch signaling pathway contributes to the CD4+/CD8+ and Th17/Treg balance in EAU rats. Our findings highlighted that the dynamic change in the CD4+/CD8+ and Th17/Treg ratio was consistent with the expression trend of Notch signaling in EAU rats, suggesting that Notch signaling may be a potentially important therapeutic target in clinical practice.
目的 围绕健康中国15项行动,构建健康中国行动评价指标体系,评估山东省16个市健康山东推进效果,识别发展短板,提出干预策略。 方法 以《健康中国行动2021―2022年考核指标体系》为基础,依据指标的重要性、代表性及可获得性,结合专家意见,识别指标体系。其后,利用逼近理想解排序法(technique for order preference by similarity to an ideal solution,TOPSIS)评估健康山东2020年的推进效果,并用仪表盘分析识别各市发展短板。 结果 健康中国指标体系包括健康危险因素控制、健康服务提供和健康结果三个维度。比较健康中国行动2030年目标值和各项指标在16市的最大值,取相对大的值作为TOPSIS的最优解,2020年山东省健康中国行动指数平均值为0.558,青岛市排名最高(0.696),菏泽市排名最低(0.386)。山东省在健康危险因素控制方面的变异系数最大(0.226),在健康结果方面的变异系数最小(0.144)。 结论 山东省16个城市已基本实现健康中国行动2022年目标值,但距离2030年目标还存在一定差距,且地区间以及不同维度间发展不平衡的问题突出,着重关注健康危险因素控制。相似文献