携带肠道衍生细菌DNA的亲炎性巨细胞驱动脊髓关节炎的自身免疫性关节炎
Benjamin Cai1, Rabina Giri2, Amy J Cameron1
1Frazer Institute, The University of Queensland, Brisbane, Australia.
JCI insight
|August 5, 2025
概括
脊椎关节炎涉及肠道细菌,在遗传敏感的个体中触发免疫反应. 这项研究揭示了肠道细菌和免疫细胞如何促进小鼠自身免疫性疾病的发展,为人类牛皮关节炎提供了洞察力.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物组研究 微生物组研究
- 自免疫性疾病 自免疫性疾病
背景情况:
- 脊椎关节炎 (SpA) 的发病包括肠道炎症和免疫系统失调.
- 遗传倾向的个体对肠道微生物群的耐受性丧失的机制尚不清楚.
研究的目的:
- 研究肠道细菌和免疫细胞相互作用在SPA的发展中的作用.
- 阐明肠道失调有助于自身免疫性关节炎和脑膜炎的机制.
主要方法:
- 使用 gnotobiotic ZAP-70W163C (SKG) 的小鼠模型,与特定的肠道细菌单联.
- 在各种组织中分析了基因表达 (Il23a,ER压力) 和细胞群 (中性粒细胞,巨细胞).
- 研究了免疫细胞 (巨细胞) 的转移,以评估它们在疾病诱导中的作用.
主要成果:
- 接受了Curdlan治疗的SKG小鼠与Parabacteroides goldsteinii或Lactobacillus murinus单一相关,发生了乳头炎,关节炎和肠炎.
- SKG小鼠表现出IL23a和ER压力基因的状上调,伴有杯状细胞损失.
- 在SKG小鼠中,细菌DNA与炎症性髓状细胞共定位,与耐受BALB/c小鼠形成鲜明对比.
- 转移的SKG巨细胞诱导了接受者小鼠的严重关节炎和Th17细胞扩张.
结论:
- 肠道细菌DNA和来自肠道的髓状细胞贩运在调节T细胞病原性方面发挥着至关重要的作用.
- 这些发现表明一种机制将肠道失调与自身免疫性关节炎联系在一起,并提供了对人类牛皮关节炎的见解.
- 来自肠道的免疫细胞,特别是巨细胞,是易感个体自身免疫性疾病的关键驱动因素.
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