皮质类固醇会损害免疫介导的肠损伤中的上皮再生
Viktor Arnhold1, Winston Y Chang1,2, Suze A Jansen3,4
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
The Journal of clinical investigation
|February 13, 2024
概括
对于胃肠道移植与宿主疾病的皮质类固醇治疗可能会通过阻碍修复来损害肠道内膜. 增加肠道再生提供了一个潜在的策略来抵消这种损害.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 再生医学是一种再生医学.
背景情况:
- 在胃肠移植与宿主疾病 (GVHD) 中,皮质类固醇治疗 (CST) 的失败导致患者的治疗结果不佳.
- 在CST期间,葡萄糖皮质体受体 (GR) 在肠上皮质中的作用尚不清楚.
- CST的目的是抑制免疫系统,但GR是广泛表达,包括在肠道.
研究的目的:
- 在GVHD的背景下,研究皮质类固醇 (CS) 对肠表皮的直接作用.
- 为了确定CST是否可以加剧免疫介导的胃肠道损伤.
- 探索减轻CS诱导损伤和促进肠道再生的策略.
主要方法:
- 使用小鼠的体内研究和使用肠道器官培养物的体外研究.
- 向小鼠和有机体培养物施用CS,治疗时间不同.
- 评估上皮细胞的增殖,密室损失,肠干细胞 (ISC) 频率和基因表达.
- 对IL-22进行干预,以评估其对CS介导损伤和再生的影响.
主要成果:
- 在小鼠和有机体培养中,CS直接降低了肠道上皮细胞的增殖和减弱了再生.
- 延迟的CST加剧了损伤,并降低了ISC频率在一种小鼠类固醇耐火 (SR) GVHD模型.
- 在涉及SR,GR缺乏T细胞或IFN-γ的有机体培养物中,CS恶化了免疫媒介损伤.
- 在GVHD的类固醇治疗小鼠中,IL-22的使用增强了STAT3活性,促进了ISC扩张,并减少了密码损失.
结论:
- 皮质类固醇可以直接损害肠道上皮质再生,如果免疫反应不能得到充分控制,可能会使GVHD的结果恶化.
- 增强上皮再生的策略,如IL-22疗法,可以抵消CS诱导的损伤.
- 将免疫抑制与促进组织修复的疗法相结合,为管理GI GVHD提供了一个有希望的临床方法.
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