Лечение хлорокина улучшает экспериментальный аутоиммунный энцефаломиэлит, сдерживая дифференциацию клеток Т и аккумуляцию PDC.
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Li Yonghai, Shao Yue, Ma Xianfen, Li Yaning, Yang Yijia, Wang Fengyuan, Yan Yushan, Hu Xiaoxi, Dai Yujie, Li Meng, Löhning Max, Shen Ping, Lin Juntang
Аннотация
Оригинал публикации
Chloroquine treatment ameliorates experimental autoimmune encephalomyelitis by inhibiting T cell differentiation and pDC accumulation.
OBJECTIVES: Chloroquine (CQ) has been used to treat rheumatoid arthritis and systemic lupus erythematosus, but its use in multiple sclerosis (MS) is limited by side effects and insufficient efficacy. To enhance treatment outcomes, understanding CQ's therapeutic mechanisms in MS is crucial. Thus, we administered CQ to mice with experimental autoimmune encephalomyelitis (EAE) and investigated its disease-ameliorating effects and underlying cellular mechanisms.
METHODS: CQ was applied intraperitoneally six days after EAE induction, immune responses, with a focus on inflammatory and regulatory T cells, as well as dendritic cells in blood, lymph nodes, spleen, and bone marrow were analyzed by flow cytometry.
RESULTS: CQ treatment significantly reduced cumulative disease score and maximal disease score in CQ-treated group. Immunohistochemical analysis of the spinal cords confirmed the reduced demyelination after CQ treatment, which is accompanied by significantly decreased infiltration of T cells, B cells, and macrophages, and less activated microglia cells. Flow cytometry analysis of peripheral lymphoid organs revealed a significant decrease of inflammatory Th17 cells, which is associated with reduced pDC and their IFN-α expression, as well as Treg cells in CQ-treated mice. Indeed, depletion of pDC alone or simultaneously with CQ treatment significantly reduced EAE severity.
CONCLUSION: Our results demonstrated that CQ treatment inhibits the development of EAE disease on one hand by enhancing the expansion of Treg in dLN and spleen, and on the other hand by inhibiting the accumulation of pDC and their IFN-α expression in the spleen and bone marrow. This joint effort restricts the level of inflammation in peripheral and later in CNS. Furthermore, developing a pDC-targeted CQ treatment will not only increase the treatment efficiency, but also largely decrease side effects.