塔卡亚苏动脉炎中的动脉壁纤维化及其治疗调制潜力
Durga Prasanna Misra1, Kritika Singh1, Aman Sharma2
1Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Frontiers in immunology
|May 31, 2023
概括
塔卡亚苏动脉炎 (TAK) 涉及动脉壁损伤和纤维化,由巨细胞和淋巴细胞等免疫细胞驱动. 将抗纤维素疗法与免疫抑制剂一起针对纤维化可能会改善治疗结果.
科学领域:
- 免疫学 免疫学 免疫学
- 血管生物学 血管生物学
- 纤维化研究 纤维化研究
背景情况:
- 塔卡亚苏动脉炎 (TAK) 的特点是动脉壁炎症和损伤,尽管免疫抑制,但可以持续存在.
- 血管纤维化是TAK的一个重要特征,通常比巨细胞动脉炎 (GCA) 更明显.
- 免疫细胞,包括M1和M2巨细胞,巨细胞和各种T-辅助17 (Th17) 淋巴细胞子集,在TAK中驱动炎症和纤维化方面发挥着至关重要的作用.
研究的目的:
- 为了阐明Takayasu动脉炎中动脉壁纤维化背后的细胞和分子机制.
- 探索潜在的治疗策略,针对TAK中的纤维化.
主要方法:
- 分析TAK动脉壁中免疫细胞透和激活标记物的分析.
- 研究参与纤维细胞激活的信号通路,包括互白素-6 (IL-6),互白素-17 (IL-17) 和转化生长因子β (TGF-β).
- 在TAK患者中,肝纤维化得分和血管损伤之间的相关性分析.
- 在体外研究评估各种药物的抗纤维素潜力.
主要成果:
- M1巨细胞分泌IL-6,过渡到分泌TGF-β和GPNMB的M2巨细胞,激活随机纤维细胞.
- 巨细胞和特定的Th17子集 (Th17.1和PD1表达的Th17) 通过IL-17,TGF-β和干扰素玛 (IFN-γ) 等介质促进纤维细胞激活.
- 在TAK中观察到,由Notch-1上调驱动的Th17和Th1淋巴细胞中的哺乳动物目标器官拉巴胺素1 (mTORC1) 的激活.
- 增强的肝纤维化得分显示了TAK.中血管损伤与血管损伤的相关性.
- 在体外研究表明,勒夫卢诺米德,托法西提尼布,巴里西提尼布和mTORC1抑制剂的潜在抗纤维作用.
结论:
- 在TAK中,动脉壁炎症后面是纤维化,由免疫细胞和信号分子的复杂相互作用介导.
- 向纤维细胞激活和纤维化通路为TAK提供了一个有希望的治疗途径.
- 涉及免疫抑制剂和抗纤维素剂的联合治疗需要在未来的临床试验中对塔卡亚苏动脉炎进行调查.
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