机械应变编程的SDC1+ 围膜纤维细胞触发CXCR4hi 中性粒细胞介导肠炎在结性脊柱炎中
Jiajie Lin1, Zepeng Su1, Yipeng Zeng1
1Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 4, 2026
概括
机械应变会在结性脊柱炎 (AS) 肠炎中触发特定的纤维细胞. 这些细胞通过CXCL5招募中性粒细胞,使疾病恶化. SOX5抑制阻断了这种途径,提供了潜在的AS治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 遗传学 是一个遗传学.
背景情况:
- 结节性脊柱炎 (AS) 是一种涉及肠炎的骨免疫疾病,但其在机械应变下的细胞机制尚未完全理解.
- 了解这些机制对于开发针对AS的向治疗至关重要.
研究的目的:
- 在实验性脊柱关节炎中阐明机械应变诱导肠炎的细胞相互作用和分子驱动因素.
- 确定结性脊柱炎的新型治疗点.
主要方法:
- 在SKG小鼠中生成后腿加载/卸载模型,以模拟机械应变.
- 单细胞RNA测序,以创建肠炎的地图.
- 计算轨迹分析以了解细胞命运的决定.
- 在体内抑制CXCL5和SOX5通路.
主要成果:
- 通过机械应变诱导的SDC1+膜纤维细胞的疾病特异性亚群的识别.
- 这些纤维细胞分泌CXCL5,招募和激活CXCR4hi中性粒细胞,这些中性粒细胞通过中性粒细胞外陷形成促进肠炎.
- SOX5控制着这些纤维细胞的生成,其抑制逆转了肠炎的发展.
- 中和CXCL5抗体治疗改善了小鼠的疾病进展.
结论:
- 机械应变诱导SDC1+纤维细胞,通过CXCL5-介导的中性粒细胞招募和激活加剧AS肠炎.
- SOX5是这种致病性纤维细胞群的关键调节者.
- 准CXCL5-CXCR4轴或SOX5为结性脊柱炎提供了潜在的治疗策略.
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