淋巴细胞激活基因 3 调节系统性硬化症患者的益菌细胞因子和I型原蛋白生产
Maithri Aspari1, Stinne Greisen2, Malene Hvid1
1Aarhus University, Aarhus, Denmark.
ACR open rheumatology
|January 11, 2026
概括
淋巴细胞激活基因3 (LAG-3) 在扩散性皮肤系统性硬化症 (dcSSc) 中具有免疫调节作用. 一种LAG-3主动性抗体可能是DCSSc的潜在治疗方法,可以减少纤维化和炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
- 纤维化研究纤维化.
背景情况:
- 扩散性皮肤系统性硬化 (dcSSc) 涉及皮肤和器官纤维化,免疫调节机制尚不清楚.
- 淋巴细胞激活基因3 (LAG-3),一个晚期检查点抑制剂,与MHCII类相互作用以抑制T细胞.
- 在dcSSc病原体中LAG-3的具体作用仍需要阐明.
研究的目的:
- 调查LAG-3在dcSSc中的作用.
- 为了比较dcSSc患者和健康对照者的可溶性LAG-3 (sLAG-3) 水平.
- 分析LAG-3在T细胞的表面表达和LAG-3主动抗体对dcSSc免疫反应和纤维化标志物的作用.
主要方法:
- 在35名dcSSc患者的血sLAG-3水平与20名HC患者的血sLAG-3水平进行比较.
- 在dcSSc患者和HC患者的CD4+和CD8+T细胞上通过流细胞计分析了表面LAG-3表达.
- 在 dcSSc PBMC 和皮肤纤维细胞共同培养物中评估了细胞因子和细胞外矩阵蛋白质的产生,这些细胞因子和细胞外矩阵蛋白质的生产被用 LAG-3 激进抗体治疗.
主要成果:
- 与HC相比,dcSSc患者的血sLAG-3水平显著降低 (降低两倍).
- 在dcSSc患者的激活CD4+和CD8+T细胞上发现了表面LAG-3表达的增加.
- 在共同培养中,LAG-3激动性抗体治疗降低了促炎细胞因子 (IFNγ,IL-4,TNFα),原蛋白,纤维素和I型IFN生物活性.
结论:
- 在dcSSc.中,LAG-3具有免疫调节作用.
- 一个LAG-3主动性抗体通过减轻免疫激活和纤维化过程,显示出作为dcSSc治疗策略的潜力.
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