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抑制JAK/STAT可以保护葡萄糖皮质体受体淘汰小鼠免受致死性疟疾诱导的低血糖和高炎症

Fran Prenen¹, Leen Vandermosten¹, Sofie Knoops¹

¹Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, 3000, Belgium.

EMBO molecular medicine

|July 23, 2025

概括

葡萄糖皮质体受体 (GR) 过程对于疟疾的耐病性至关重要,防止致命的低血糖和细胞因子风暴. 用ruxolitinib准JAK/STAT通路通过管理这些并发症来改善生存率.

科学领域:

免疫学免疫学免疫学
代谢性疾病是一种代谢性疾病.
疟疾研究疟疾研究

背景情况:

疾病耐受性机制在感染期间限制宿主损伤,但在疟疾中人们对其了解甚少.
这些机制对于预防严重疟疾和死亡率至关重要.

研究的目的:

为了研究葡萄糖皮质体受体 (GR) 介导的过程在Plasmodium chabaudi AS疟疾中的作用.
探索GR信号,代谢功能障碍和超炎症之间的联系.

主要方法:

使用一种小鼠模型,以GR删除的Plasmodium chabaudi AS感染.
分析了肝脏和脏的代谢概况,重点关注葡萄糖代谢和基因表达.
研究了JAK/STAT通路和细胞因子表达.
评估了JAK1/2抑制剂ruxolitinib的治疗潜力.

主要成果:

在感染的小鼠中,GR删除导致致命的低血糖和细胞因子风暴.
低血糖症的特征是肝脏和脏代谢受损,葡萄糖摄取量增加和葡萄糖原性基因表达减少.
低血糖状态与JAK/STAT通路过度激活和过度的细胞因子产生相关.
卢克索利提尼布治疗通过减轻低血糖和高炎症,改善了生存率.

结论:

GR介导的过程对于疟疾的耐病性至关重要,调节葡萄糖代谢和炎症.
在严重疟疾中,GR信号,STAT3激活,细胞因子表达和葡萄糖代谢之间存在一种新的联系.
卢克索利提尼布作为治疗严重疟疾代谢并发症的辅助疗法具有前景.

关键词:

葡萄糖皮质体受体葡萄糖皮质体受体低血糖症是一种低血糖症.疟疾:疟疾是一种疾病.卢克索利提尼布 (Ruxolitinib) 是一种药物.宽容是一种宽容.

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