The First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health, Japan, Kitakyushu 807-8555, Japan; Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu 879-5593, Japan.
The First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health, Japan, Kitakyushu 807-8555, Japan; Mitsubishi Tanabe Pharma, Yokohama 227-0033, Japan.
Clin Immunol. 2018 Oct;195:1-7. doi: 10.1016/j.clim.2018.07.003. Epub 2018 Jul 4.
Hydroxychloroquine is widely used for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Although B cells contribute to the pathogenesis of these diseases, the action of hydroxychloroquine on B cells remains unclear. Here we examined the effects of hydroxychloroquine on functions of B cell subsets. Hydroxychloroquine efficiently inhibited the mammalian target of rapamycin complex 1, differentiation of CD19IgDCD27 class-switched memory B cells to plasmablasts and their IgG production, under stimulation with CpG, a Toll-like receptor (TLR)-9 ligand. Hydroxychloroquine also inhibited CpG-induced production of interleukin-6 and tumor necrosis factor-α in B cell subsets. Taken together, hydroxychloroquine markedly suppresses the TLR9-mediated human B cell functions during inflammatory processes. Based on our results, we believe that hydroxychloroquine can be beneficial in the treatment of B cell-mediated autoimmune diseases.
羟氯喹被广泛用于治疗系统性红斑狼疮和类风湿关节炎等自身免疫性疾病。尽管 B 细胞有助于这些疾病的发病机制，但羟氯喹对 B 细胞的作用尚不清楚。在这里，我们研究了羟氯喹对 B 细胞亚群功能的影响。在 CpG（一种 Toll 样受体 (TLR)-9 配体）刺激下，羟氯喹可有效抑制哺乳动物雷帕霉素靶蛋白复合物 1 的活性，从而阻止 CD19IgDCD27 类别转换记忆 B 细胞分化为浆母细胞及其 IgG 的产生。羟氯喹还抑制 CpG 诱导的 B 细胞亚群中白细胞介素-6 和肿瘤坏死因子-α的产生。综上所述，羟氯喹可显著抑制 TLR9 介导的人类 B 细胞在炎症过程中的功能。基于我们的研究结果，我们认为羟氯喹可能对 B 细胞介导的自身免疫性疾病的治疗有益。
