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对肠道病原体的免疫耐受性介导c-MAF依赖的调节性T细胞
Mo Xu1, Maria Pokrovskii1, Yi Ding2
1Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
Nature
|February 8, 2018
概括
宿主对病原体Helicobacter hepaticus的耐受性依赖于c-MAF依赖的调节性T细胞 (iTreg),可以抑制炎症性T辅助细胞17 (TH17),从而预防自身免疫性疾病.
科学领域:
- 免疫学
- 微生物学
- 遗传学
背景情况:
- 自身免疫性疾病涉及微生物和宿主遗传因素.
- 像Helicobacter物种一样, 病原生物可以引发慢性炎症和致病性T细胞.
- 在健康个体中抑制致病性T细胞的机制尚不清楚.
研究的目的:
- 研究宿主对病原生物的耐受性机制.
- 确定调节性T细胞 (Tregs) 在控制T辅助细胞17 (TH17) 反应中的作用.
- 阐明涉及Treg功能和免疫平衡的转录因子.
主要方法:
- 野生型和缺乏IL-10的小鼠被Helicobacter hepaticus殖民.
- 分析T细胞分化,包括RORγt+FOXP3+iTreg和TH17细胞.
- 在Treg细胞中转录因子c-MAF和RORγt的遗传失活.
主要成果:
- 在野生型小鼠中,H. hepaticus诱导了表达RORγt的iTreg细胞,抑制了TH17细胞.
- 在缺乏IL-10的小鼠中,在H. hepaticus的殖民化过程中,TH17细胞呈现扩张.
- 在Tregs中缺乏c-MAF会损害iTreg功能,导致TH17细胞积累和自发性结肠炎.
- 在Tregs中RORγt的失活对免疫平衡的影响很小,并没有引起炎症.
结论:
- 通过抑制TH17细胞的c-MAF依赖的iTreg细胞来调节宿主对H.
- 这种c-MAF依赖的iTreg-TH17平衡的失调使得对病原体反应的T细胞能够驱动炎症性肠病.
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