RNF2介导H2A泛素化，通过抑制小鼠单核细胞-巨噬细胞转换促进结肠炎
RNF2 mediates H2A ubiquitination to promote colitis via suppressing monocyte-macrophage transition in mice.
摘要(中文译文)
单核细胞-巨噬细胞转化在炎症性肠病中存在失调。尽管多梳抑制复合物对维持细胞身份至关重要，但其在结肠炎中的具体作用尚不明确。在此，我们证明Ring finger蛋白2（多梳抑制复合物1的核心催化亚基）调控结肠炎期间的单核细胞-巨噬细胞转化。该蛋白在溃疡性结肠炎期间的未成熟结肠及循环单核细胞中高表达。髓系特异性缺陷小鼠表现出实验性结肠炎减轻、单核/巨噬细胞平衡恢复以及抗肿瘤坏死因子α疗效改善。机制上，Ring finger蛋白2通过组蛋白H2A赖氨酸119单泛素化抑制Runt相关转录因子3的表达。这破坏了对免疫球蛋白κJ区重组信号结合蛋白（Notch通路的中心激活因子）的抑制，从而加剧炎症。沉默该轴可显著抑制促炎反应，调控单核-巨噬细胞转化。这些发现揭示Ring finger蛋白2破坏结肠炎期间的单核细胞-巨噬细胞转化，为结肠炎治疗提供了见解。
Abstract
Monocyte-macrophage transition is dysregulated in inflammatory bowel disease. While polycomb repressive complexes are crucial for maintaining cellular identity, their specific roles in colitis are poorly defined. Here, we show that Ring finger protein 2, a core catalytic subunit of polycomb repressive complex 1, regulates the monocyte-macrophage transition during colitis. It is highly expressed in the immature colon and circulating monocytes during ulcerative colitis. And mice with myeloid-specific deficiency exhibited attenuated experimental colitis, restored monocyte/macrophage balance, and improved anti-tumor necrosis factor alpha efficacy. Mechanistically, Ring finger protein 2 represses Runt-related transcription factor 3 expression via histone H2A lysine 119 monoubiquitination. This disrupts the inhibition of the recombination signal-binding protein for the immunoglobulin kappa J region, the central activator of the Notch pathway, thereby exacerbating inflammation. Silencing of the axis markedly inhibited proinflammatory responses, regulating monocyte-macrophage transition. These findings reveal that Ring finger protein 2 disrupts the monocyte-macrophage transition during colitis, offering insights into colitis treatments.
如何引用
AMA
Fanyi Meng, Tao Zhang, Xiangyu Meng, Wenjing Zhao, Ge Jin, Yingying Zhao, et al. RNF2 mediates H2A ubiquitination to promote colitis via suppressing monocyte-macrophage transition in mice.. Nature communications. 2026; doi:10.1038/s41467-026-74962-5.
APA
Fanyi Meng, Tao Zhang, Xiangyu Meng, Wenjing Zhao, Ge Jin, Yingying Zhao, et al (2026). RNF2 mediates H2A ubiquitination to promote colitis via suppressing monocyte-macrophage transition in mice.. Nature communications. https://doi.org/10.1038/s41467-026-74962-5
GB/T 7714
Fanyi Meng, Tao Zhang, Xiangyu Meng, Wenjing Zhao, Ge Jin, Yingying Zhao, et al. RNF2 mediates H2A ubiquitination to promote colitis via suppressing monocyte-macrophage transition in mice.[J]. Nature communications, 2026 doi:10.1038/s41467-026-74962-5.
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