Institute for Advanced Biosciences, Université Grenoble Alpes, Inserm U 1209, CNRS, UMR 5309, 38000, Grenoble, France.
Etablissement Français du Sang Auvergne-Rhône-Alpes, Research and Development Lab, 29 Av Maquis du Grésivaudan, 38701, La Tronche, France.
J Transl Med. 2019 Sep 18;17(1):312. doi: 10.1186/s12967-019-2066-1.
Despite major advances in rheumatoid arthritis outcome, not all patients achieve remission, and there is still an unmet need for new therapeutic approaches. This study aimed at evaluating in a pre-clinical murine model the efficacy of extracorporeal photopheresis (ECP) in the treatment of rheumatoid arthritis, and to provide a relevant study model for dissecting ECP mechanism of action in autoimmune diseases.
DBA/1 mice were immunized by subcutaneous injection of bovine collagen type II, in order to initiate the development of collagen-induced arthritis (CIA). Arthritic mice received 3 ECP treatments every other day, with psoralen + UVA-treated (PUVA) spleen cells obtained from arthritic mice. Arthritis score was measured, and immune cell subsets were monitored.
ECP-treated mice recovered from arthritis as evidenced by a decreasing arthritic score over time. Significant decrease in the frequency of Th17 cells in the spleen of treated mice was observed. Interestingly, while PUVA-treated spleen cells from healthy mouse had no effect, PUVA-treated arthritic mouse derived-spleen cells were able to induce control of arthritis development.
Our results demonstrate that ECP can control arthritis in CIA-mice, and clarifies ECP mechanisms of action, showing ECP efficacy and Th17 decrease only when arthritogenic T cells are contained within the treated sample. These data represent a pre-clinical proof of concept supporting the use of ECP in the treatment of RA in Human.
尽管类风湿关节炎的治疗取得了重大进展，但并非所有患者都能达到缓解，仍有新的治疗方法需要探索。本研究旨在通过建立一种临床前的关节炎小鼠模型，评估体外光化学疗法（ECP）在治疗类风湿关节炎中的疗效，并为探讨 ECP 在自身免疫性疾病中的作用机制提供一个相关的研究模型。
DBA/1 小鼠通过牛 II 型胶原的皮下注射来引发胶原诱导的关节炎（CIA）。关节炎小鼠每隔一天接受 3 次 ECP 治疗，使用从关节炎小鼠中提取的经补骨脂素+长波紫外线（PUVA）处理的脾细胞。通过关节炎评分来评估疾病的进展，监测免疫细胞亚群的变化。
ECP 治疗的小鼠关节炎得到缓解，随着时间的推移，关节炎评分逐渐下降。治疗组小鼠脾脏中的 Th17 细胞频率明显降低。有趣的是，虽然健康小鼠的 PUVA 处理脾细胞没有效果，但来自关节炎小鼠的 PUVA 处理脾细胞能够诱导关节炎的控制。
我们的研究结果表明，ECP 可以控制 CIA 小鼠的关节炎，阐明了 ECP 的作用机制，表明只有在治疗样本中包含致关节炎 T 细胞时，ECP 才具有疗效并能降低 Th17 细胞的频率。这些数据为 ECP 在人类类风湿关节炎治疗中的应用提供了临床前的概念验证。
