特定于H3K27的脱甲基酶协调了肠道ILC3s的表型和功能性可塑性
Xianzhi Gao1, Xin Shen2, Qianying Xu3
1Institute of Immunology and Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liang Zhu Laboratory, Zhejiang University Medical Center, Hangzhou, China; Zhejiang University School of Medicine, Hangzhou, China.
Cell reports
|January 20, 2026
概括
基因组脱甲基酶UTX和JMJD3调节3组先天性淋巴细胞 (ILC3) 的可塑性. 它们的缺失会损害NKp46+ ILC3s,同时促进CCR6+ ILC3s,影响粘膜免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 第三组先天性淋巴细胞 (ILC3s) 对于粘膜免疫至关重要,并表现出可塑性.
- 表观遗传机制,包括基因组修饰,控制ILC3的分化和功能.
研究的目的:
- 在ILC3专业化中研究组织素脱甲基酶UTX和JMJD3在ILC3专业化中的作用.
- 阐明控制ILC3子集平衡和功能的表观遗传机制.
主要方法:
- 使用单细胞分析分析ILC3分化轨迹.
- 在目标下使用Cleave和标记 (CUT&Tag) 来映射UTX绑定站点.
- 进行逆转录病毒复制,以评估TCF7的功能.
主要成果:
- UTX和JMJD3缺乏导致NKp46+ ILC3s的耗尽和CCR6+ ILC3s的扩张.
- 通过UTX/JMJD3剥离的表观遗传重编程改变了ILC3谱系的承诺.
- UTX通过在其增强剂区域中去甲基化H3K27me3来直接调节Tcf7的表达.
- 在ILC3分化中,TCF7充当UTX的关键下游效应因子.
结论:
- UTX和JMJD3是ILC3子集平衡和功能的关键表观遗传调节者.
- 这些发现突出了UTX-TCF7轴控制粘膜免疫力的作用.
- 准UTX/JMJD3为ILC3相关的炎症性疾病提供了潜在的治疗策略.
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