在TGFβ信号传递和TNF刺激之间相互抑制可以微调巨细胞的炎症反应
Yuhan Xia1,2, Kazuki Inoue1,2, Ting Zheng1,2
1Arthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, New York, USA.
瘤亡因子 (TNF) 通过表观遗传和RBP-J机制抑制巨细胞中的转化生长因子β (TGFβ) 信号,增加炎症. 增强TGFβ信号传递可能提供新的炎症控制策略.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 炎症是疾病的核心,TNF和TGFβ等细胞因子协调其过程.
- 巨细胞中TNF和TGFβ信号传递之间的相互作用仍然不清楚,特别是在炎症调节方面.
研究的目的:
- 阐明TNF与TGFβ信号通信以控制巨细胞炎症的机制.
- 调查TGFβ信号传递作为对抗TNF诱导炎症的恒常路径的作用.
主要方法:
- 使用了条件TGFβ受体淘汰小鼠,人类细胞,RNAseq,ATACseq和Cut & Run-seq.
- 采用遗传和分子/细胞方法来分析TNF-TGFβ通路相互作用.
主要成果:
- TGFβ信号传递作为一种恒常通路,限制由TNF刺激的巨细胞中不受控制的炎症.
- TNF通过新的表观遗传和RBP-J介导机制抑制TGFβ信号传递.
- 这种相互抑制通过减少TGFβ的对抗作用来增强TNF的促炎作用.
结论:
- TNF和TGFβ信号之间的平衡对于确定炎症严重程度至关重要.
- 针对TGFβ信号的治疗方法是治疗TNF驱动炎症的有希望的策略.
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