RORγt+APCs需要一个不同的cis-regulatory元素来指导对饮食抗原的耐受性
Xiaohuan Guo1, Jie Zhao2, Jiacheng Hao2
1Institute for Immunology, School of Medicine, Tsinghua University.
Research square
|August 6, 2025
概括
RORγt+抗原呈现细胞 (APC) 对于口服耐受性至关重要. 一个特定的调节元件,OCR369,控制这些细胞中的RORγt表达,维持肠道平衡,防止过敏.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 胃肠病学 胃肠病学
背景情况:
- 口服耐受性可以防止对无害抗原的肠道炎症.
- RORγt+抗原呈现细胞 (APC) 诱导微生物群特定的Tregs,但它们在饮食抗原耐受性中的作用尚不清楚.
研究的目的:
- 研究RORγt表达在RORγt+APC中的调节机制.
- 确定RORγt+ APCs在调解口服耐受性对饮食抗原中的作用.
主要方法:
- 在RORγt+细胞类型中对Rorc基因位点进行ATAC-seq比较分析.
- 确定和功能分析一个 cis 调节元件 (OCR369).
- 在小鼠中通过CRISPR中介OCR369的删除以及免疫细胞群和口服耐受性的评估.
主要成果:
- OCR369通过RUNX3相互作用和染色质循环,专门调节ILC3s和其他RORγt+APC中的RORγt表达.
- 删除OCR369减少了RORγt+ APCs和ILC3s,导致RORγt+ Tregs减少和小肠自发性炎症.
- 由于减少了RORγt+APCs,饮食和微生物群特异性RORγt+ Tregs的发育受损导致口服耐受性丧失和过敏敏感性增加.
结论:
- 在涉及OCR369的RORγt+ APC中确定了RORγt表达的新型调节机制.
- RORγt+ APCs在调解口服耐受性对饮食抗原和维持肠道健康方面发挥着关键作用.
- RORγt+ APCs的失调有助于失去口服耐受性和增加过敏敏感性.
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