需要Rorγt阳性树突细胞来诱导外周调节T细胞对口服抗原的反应
Patrick Fernandes Rodrigues1, Shitong Wu1, Tihana Trsan1
1Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
Cell
|April 4, 2025
概括
研究人员发现淋巴状RORγt+树突细胞 (DCs) 对于诱导维持肠道免疫耐受性的调节性T细胞 (Tregs) 是至关重要的. 它们的消耗会降低口服耐受性,并促进过敏反应.
科学领域:
- 免疫学
- 胃肠病学
- 细胞生物学
背景情况:
- 肠道免疫系统依赖于外围衍生的RORγt+调节性T细胞 (pTregs) 来维持对食物抗原和肠道微生物群的耐受性.
- 包括树突细胞 (DC) 亚组和3型先天性淋巴细胞 (ILC) 在内的RORγt+抗原呈现细胞 (APC) 参与pTreg诱导.
研究的目的:
- 调查RORγt+ DCs在肠道免疫恒温的特定作用.
- 阐明RORγt+ DCs与ILC3s在维持免疫耐受性的关系.
主要方法:
- 通过向Rorc基因的cis调节元件,开发一种具有减少RORγt+APC的转基因小鼠模型.
- 使用单细胞RNA测序和流细胞测量来确认细胞群变化.
- 使用血统追踪来确定RORγt+ DCs的发育起源.
主要成果:
- 在修改后的小鼠中确认了RORγt+ DC子集和ILC3s的耗尽.
- 观察到pTregs的次要降低和口服抗原耐受性受损.
- 发现T助手2 (Th2) 细胞的增加,表明过敏反应的转变.
- 证明单独的ILC3缺乏不会导致这些异常.
- 在RORγt+ DCs和ILC3s之间发现了共享的淋巴原点.
结论:
- 在诱导pTreg和维持肠道免疫耐受性方面,RORγt+ DCs是必不可少的.
- 淋巴细胞RORγt+ DC在预防食物过敏和炎症方面发挥着至关重要的作用.
- 了解RORγt+ DC-pTreg轴为免疫媒介肠道疾病提供了潜在的治疗点.
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