Tregs 耗竭通过调节脑梗死后继发的 IL-10/GXP4 加重星形胶质细胞的激活。
Tregs depletion aggravates activation of astrocytes by modulating IL-10/GXP4 following cerebral infarction.
机构信息
Emergency Department, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
General Medical Department, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
出版信息
Front Immunol. 2023 Aug 9;14:1255316. doi: 10.3389/fimmu.2023.1255316. eCollection 2023.
BACKGROUND
Tregs plays a critical role in the development of secondary injuries in diseases. Accumulating evidence suggests an association between ischemic stroke and renal dysfunction; however, the underlying mechanisms remain unclear. This study aimed to investigate the potential of Tregs in inhibiting the activation of astrocytes after focal cerebral infarction.
METHODS
This study aimed to investigate the renal consequences of focal cerebral ischemia by subjecting a mouse model to transient middle cerebral artery occlusion (tMCAO). Subsequently, we assessed renal fibrosis, renal ferroptosis, Treg infiltration, astrocyte activation, as well as the expression levels of active GPX4, FSP1, IL-10, IL-6, and IL-2 after a 2-week period.
RESULTS
In the tMCAO mouse model, depletion of tregs protected against activation of astrocyte and significantly decreased FSP1, IL-6, IL-2, and NLRP3 expression levels, while partially reversing the changes in Tregs. Mechanistically, tregs depletion attenuates renal fibrosis by modulating IL-10/GPX4 following cerebral infarction.
CONCLUSION
Tregs depletion attenuates renal fibrosis by modulating IL-10/GPX4 following cerebral infarction.
背景
调节性 T 细胞（Tregs）在疾病的继发性损伤发展中发挥着关键作用。越来越多的证据表明，缺血性脑卒中与肾功能障碍之间存在关联；然而，其潜在机制尚不清楚。本研究旨在探讨 Tregs 抑制局灶性脑梗死后星形胶质细胞激活的潜力。
方法
本研究通过对小鼠模型进行短暂性大脑中动脉闭塞（tMCAO）来研究局灶性脑缺血的肾脏后果。随后，我们评估了 2 周后肾纤维化、肾铁死亡、Treg 浸润、星形胶质细胞激活以及活性 GPX4、FSP1、IL-10、IL-6 和 IL-2 的表达水平。
结果
在 tMCAO 小鼠模型中，Tregs 耗竭可防止星形胶质细胞激活，并显著降低 FSP1、IL-6、IL-2 和 NLRP3 的表达水平，同时部分逆转 Tregs 的变化。机制上，Tregs 耗竭通过调节脑梗死后脑内的 IL-10/GPX4 来减轻肾纤维化。
结论
Tregs 耗竭通过调节脑梗死后脑内的 IL-10/GPX4 来减轻肾纤维化。
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