工程 Escherichia coli 尼斯尔 1917 携带PD1激动剂通过局部免疫调节解决肠道炎症
Mengyuan Hu1, Tingting Li1, Mengmeng Xu2
1Department of Pathology, The First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection& School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Cancer institute, Suzhou medical college, Soochow University, Suzhou, Jiangsu 215123, China.
ACS applied materials & interfaces
|May 9, 2025
概括
这项研究开发了一种益生菌Escherichia coli Nissle 1917 (EcN) 疗法,以抑制异常的T细胞激活,减少肠道炎症并促进小鼠模型中的肠道修复.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 微生物学 微生物学
背景情况:
- 肠道炎症通常是由免疫失衡引起的,缺乏有效的治疗方法.
- 辐射诱导的肠损伤模型显示T细胞的异常激活是炎症的关键驱动因素.
- 针对PD1信号通路提供了一个潜在的策略来调节T细胞的反应.
研究的目的:
- 为了研究PD1激动剂显示益生菌Escherichia coli Nissle 1917 (EcNMP1-M) 对辐射诱导肠炎的治疗潜力.
- 在小鼠肠道损伤模型中评估 EcNMP1-M 的抗炎和肠道修复作用.
- 评估 EcNMP1-M 对肠道微生物群组成和多样性的影响.
主要方法:
- 使用了辐射诱导的肠损伤模型和两个额外的小鼠模型.
- 在Eudragit L100-55中封装的工程EcNMP1-M以通过细菌外膜囊泡 (OMV) 表达PD1激动剂.
- 评估了免疫激活,炎症性细胞因子,肠上皮质屏障完整性和肠道微生物群多样性 (16S rDNA测序).
主要成果:
- 通过向PD1路径,ecNMP1-M显著抑制了过度的免疫激活,并减少了炎症性细胞因子.
- 用 EcNMP1-M 治疗促进了对肠上皮质屏障完整性至关重要的蛋白质的表达,改善了肠道功能.
- 在结肠炎模型中,EcNMP1-M增强了肠道微生物群的多样性,增加了有益细菌,减少了有害细菌.
结论:
- 在临床前模型中,EcNMP1-M显示出显著的抗炎和肠道修复能力.
- 这种基于益生菌的疗法在辐射引起的肠炎和炎症性肠病中显示出局部免疫抑制的前景.
- 这些发现表明,这种基于EcN的新型治疗策略有可能用于临床应用.
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