REV-ERB通过Bhlhe40-c-Maf轴调节RORγt+调节性T细胞的特异性和功能
Xianting Hu1,2, Zhi Liu2,3, Yao Li3
1Department of Otolaryngology, Head and Neck Surgery, Eye and ENT Hospital, Fudan University, Shanghai, China.
The Journal of experimental medicine
|December 8, 2025
概括
转录抑制剂REV-ERB对于控制肠道炎症的专门结肠调节T (Treg) 细胞至关重要. 它的缺失会通过损害Treg功能而使炎症性肠病恶化.
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:
- 表达RORγt的Foxp3+调节性T (Treg) 细胞对于控制肠道炎症至关重要.
- 驱动RORγt+Foxp3+ Treg专业化的具体因素尚未完全理解.
研究的目的:
- 研究转录抑制剂REV-ERB在结肠RORγt+Foxp3+Treg细胞的分化和功能中的作用.
- 阐明REV-ERB影响Treg专业化和肠道炎症的分子机制.
主要方法:
- 使用化学诱导性结肠炎的小鼠模型 (TNBS和oxazolone).
- 分析了与Treg分化和功能相关的基因表达和蛋白质水平.
- 调查了涉及REV-ERB,Bhlhe40和c-Maf的监管轴.
主要成果:
- 在小鼠模型中,REV-ERB缺乏会显著恶化肠道炎症.
- 发现REV-ERB可以抑制Bhlhe40,从而通过c-Maf促进RORγt的表达.
- REV-ERB/Bhlhe40-c-Maf通路调节关键的Treg基因 (IL-10,CTLA-4) 并抑制IL-17A的产生.
结论:
- REV-ERB对于结肠RORγt+Foxp3+Treg细胞的分化和功能至关重要.
- 在REV-ERB下游的Bhlhe40-c-Maf轴在Treg专业化中起着至关重要的作用.
- 针对REV-ERB或其下游途径可能为炎症性肠道疾病提供治疗策略.
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