在糖尿病脑病变中,Th22细胞促进从平稳的微质细胞过渡到反应性的微质细胞
Sheng-Xue Yu1,2, Hong Dan Yu1,2, Yu-Fei Wang1,2
1Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou, China.
Acta diabetologica
|December 4, 2024
概括
在糖尿病脑病 (DE) 中,Th22细胞透到大脑中,释放IL-22.2. 这种细胞因子激活微质,导致炎症和恶化DE的认知缺陷.
科学领域:
- 神经免疫学 神经免疫学
- 内分泌学 在内分泌学.
- 免疫学 免疫学 免疫学
背景情况:
- 糖尿病脑病变 (DE) 是糖尿病 (DM) 的严重并发症,其病因不明.
- Th22细胞是CD4+T细胞的一个子集,与炎症和自身免疫性疾病有关.
- Th22细胞在DE病原发生中的作用仍然在很大程度上是未知的.
研究的目的:
- 研究Th22细胞及其细胞因子产物IL-22在糖尿病脑病变的发展中的作用.
- 阐明Th22细胞和IL-22在2型糖尿病 (T2DM) 的小鼠模型中影响大脑炎症和认知功能的机制.
主要方法:
- 建立了一个T2DM小鼠模型,并在高葡萄糖条件下使用Th22细胞和微质细胞的体外共养系统.
- 通过莫里斯水迷宫 (MWM) 测试评估认知功能,并通过埃文斯蓝色扩散评估血脑屏障 (BBB) 完整性.
- 通过免疫光检测了Th22细胞和IL-22受体,并使用西布洛特分析测量了炎症蛋白质表达.
主要成果:
- 观察到Th22细胞穿越BBB进入海马,分泌IL-22,与学习和记忆障碍相关.
- 在DE模型中,IL-22促进了同居微质细胞向反应性表型的过渡,从而增加了神经炎症.
- 在体外,在高葡萄糖条件下与微质一起培养的Th22细胞增强了促炎性细胞因子的产生,并诱导了微质激活.
- 通过IL-22Rα1在微质上传递IL-22信号被确定为微质诱导炎症的关键驱动因素,IL-22BP作为抑制剂.
结论:
- Th22细胞通过迁移到海马体并释放IL-22.2,从而促进DE.
- IL-22驱动微质激活和炎症,加剧认知缺陷并加速DE的进展.
- 准Th22细胞-IL-22轴是一个潜在的治疗策略,用于管理糖尿病脑病变.
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