ObjectivesRheumatoid arthritis (RA) synovitis frequently persists despite cytokine-targeted therapies, suggesting the existence of pathogenic stromal programs that sustain chronic inflammation independently of canonical immune pathways. Although synovial fibroblasts (SF) are increasingly implicated in treatment resistance, the pathogenic fibroblast states driving refractory disease and their therapeutic vulnerabilities remain poorly defined.
1. 目标：类风湿关节炎（RA）滑膜炎常在细胞因子靶向治疗后持续存在，提示存在独立于经典免疫通路、维持慢性炎症的致病性基质程序。尽管滑膜成纤维细胞（SF）在治疗抵抗中的作用日益凸显，但驱动难治性疾病的致病性成纤维细胞状态及其治疗靶点仍不明确。
MethodsWe integrated multimodal single-cell and spatial profiling of synovial tissue from 54 patients with RA with prospective treatment-response data and functional studies in human fibroblasts and experimental arthritis models.
2. 方法：我们整合了54例RA患者滑膜组织的多模态单细胞与空间分析数据，并结合前瞻性治疗反应数据及人成纤维细胞与实验性关节炎模型的功能研究。
Yoshihara, R. et al. · CC-BY 4.0