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便微生物群移植通过ARDS大鼠的JAK/STAT途径调节Th17/Treg平衡

Dongwei Zhang^1,2,3,4, Biying Dong^1,2,3,4, Jie Chen^1,5

¹Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.

Advanced biology

|June 27, 2025

概括

便微生物种移植 (FMT) 通过恢复免疫平衡,有效地治疗大鼠的急性呼吸困扰综合征 (ARDS). FMT通过调节T-辅助17/调节T细胞平衡和抑制JAK/STAT通路来缓解肺损伤.

科学领域:

免疫学免疫学免疫学
胃肠病学胃肠病学
肺部病理学肺部病理学

背景情况:

急性呼吸窘迫综合征 (ARDS) 是一种严重的炎症性肺部疾病,治疗选择有限.
肠道微生物群及其代谢产物在全身炎症和免疫反应中起着至关重要的作用.
在T助手17 (Th17) 和调节性T (Treg) 细胞的不平衡,以及JAK/STAT通路的激活,都与ARDS的发病有关.

研究的目的:

为了研究便微生物群移植 (FMT) 的治疗效果,在一个由脂聚糖 (LPS) 诱导的ARDS的老鼠模型中.
评估FMT对Th17/Treg细胞平衡和Janus激酶/信号转换器和转录激活器 (JAK/STAT) 信号通路的影响.
评估FMT对肺部和肠道组织病理学以及全身炎症标志物的影响.

主要方法:

在大鼠中通过鼻内LPS灌注建立了一个ARDS模型.
干预包括FMT,Treg细胞枯竭和JAK抑制剂.
评估包括肺部和肠道组织病理学,流动细胞计 (Th17/Treg细胞),qPCR,西部斑点,细胞因子ELISA和斯皮尔曼相关性分析.

主要成果:

FMT和JAK抑制剂显著降低了LPS诱导的肺损伤,包括膜破坏和炎症.
FMT治疗恢复了Th17/Treg细胞平衡,并抑制了JAK/STAT通路的活性.
在血清中,FMT降低了促炎性细胞因子 (例如IL-6,IL-17A) 和增加了抗炎性细胞因子 (例如IL-10),表明恢复了免疫平衡.

结论:

便微生物群移植显示出对ARDS的显著治疗潜力.
在LPS诱导的ARDS中,FMT通过调节Th17/Treg平衡和抑制JAK/STAT通路来缓解肺和肠损伤.
通过FMT准肠道微生物群为管理ARDS和相关炎症状况提供了一个有希望的策略.

关键词:

这就是JAK/STAT.在Th17细胞中.急性呼吸困扰综合征是什么便微生物群移植监管T细胞的监管性T细胞

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The JAK-STAT Signaling Pathway

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...