骨质细胞USP26通过内源性托芬代谢产物调节B淋巴发育
Wenkai Ye1, Guoqing Tang2, Jiyuan Tang1
1Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
Journal of advanced research
|February 13, 2026
概括
骨质母细胞USP26缺乏通过破坏托代谢和B细胞发育,损害骨形成和免疫功能. 在骨质疏松症模型中,通过外体恢复USP26可以改善骨密度和抗感染能力.
科学领域:
- 免疫学 免疫学 免疫学
- 骨生物学 骨生物学 骨生物学
- 代谢调节 代谢调节 代谢调节
背景情况:
- 骨质损失与免疫系统衰退有关.
- 骨质母细胞调节骨和免疫细胞,但机制尚不清楚.
研究的目的:
- 探索骨质细胞退化如何导致骨质疏松症的免疫衰退.
- 为了确定链接骨损失和免疫功能障碍的分子机制.
主要方法:
- 分析了骨质疏松患者和小鼠的免疫细胞.
- 在骨质细胞和骨中评估USP26表达.
- 评估了 Usp26 淘汰赛小鼠的骨形成,B 淋巴发育和败血症存活率.
- 使用转录学,代谢学和托代谢物实验.
- 测试了USP26修饰外体的治疗潜力.
主要成果:
- 在骨质母细胞中USP26下调与骨质损失和免疫功能障碍有关.
- 减少USP26会损害骨质母细胞分化,并降解IL4I1.1.
- 这扰乱了托代谢轴,减少了酸 (IAA) 和危害B型淋巴发育.
- 缺乏USP26的小鼠显示B细胞减少,败血症死亡率增加.
- 通过外体介导的USP26输送恢复了骨形成,B细胞生产和抗感染能力.
结论:
- 骨质细胞USP26双重调节骨形成和免疫激活.
- 针对USP26/IL4I1-AHR轴提供了与年龄相关的骨质损失中免疫缺陷的治疗策略.
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