系统性红斑狼疮（SLE）是一种常见的自身免疫性疾病，其发病机制主要涉及B细胞通过滤泡辅助性T（Tfh）细胞异常激活产生致病抗体，需要更有效、安全的治疗方法。二氢青蒿素（DHA）是青蒿素的主要活性成分，具有免疫抑制作用。本研究体外实验证实DHA抑制Tfh细胞诱导，削弱其对B细胞分化的辅助功能；此外，DHA直接抑制B细胞活化、分化和抗体产生。此外，建立了 SLE 小鼠模型，我们证实 DHA 显着减轻 SLE 和狼疮性肾炎的症状，并降低血清免疫球蛋白 (Ig)G、IgM、IgA 和抗 dsDNA 水平。此外，DHA 降低了总 Tfh 细胞、活化 Tfh 细胞和 B 细胞淋巴瘤 6 的频率，以及脾脏和淋巴结 Tfh 细胞中白细胞介素 (IL)-21 的水平，以及 B 细胞、生发中心的水平脾脏、淋巴结和肾脏中的 B 细胞和浆细胞。此外，DHA通过阻断IL-2诱导的T细胞激酶（ITK）信号及其下游核因子（NF）-κB、活化T细胞的核因子和激活蛋白1途径来抑制Tfh细胞，并直接抑制B细胞通过阻断布鲁顿酪氨酸激酶 (BTK) 信号传导以及下游 NF-κB 和 Myc 通路。总体而言，我们的结果表明，DHA 通过阻断 ITK 信号传导抑制 Tfh 细胞，并通过阻断 BTK 信号传导直接抑制 B 细胞。因此，减少致病性抗体的产生可能会有效治疗 SLE。© 2024。韩国药学会。

Systemic lupus erythematosus (SLE) is a common autoimmune disease, and its pathogenesis mainly involves the aberrant activation of B cells through follicular helper T (Tfh) cells to produce pathogenic antibodies, which requires more effective and safe treatment methods. Dihydroartemisinin (DHA) is the main active ingredient of artemisinin and has immunosuppressive effects. In this study, in vitro experiments confirmed that DHA inhibited Tfh cell induction and weakened its auxiliary function in B cell differentiation; furthermore, DHA directly inhibited B cell activation, differentiation, and antibody production. Furthermore, a mouse model of SLE was established, and we confirmed that DHA significantly reduced the symptoms of SLE and lupus nephritis, and decreased serum immunoglobulin (Ig)G, IgM, IgA, and anti-dsDNA levels. Moreover, DHA reduced the frequencies of total Tfh cells, activated Tfh cells, and B cell lymphoma 6, and interleukin (IL)-21 levels in Tfh cells from the spleen and lymph nodes, as well as the levels of B cells, germinal center B cells, and plasma cells in the spleen, lymph nodes, and kidneys. Additionally, DHA inhibited Tfh cells by blocking IL-2-inducible T cell kinase (ITK) signaling and its downstream nuclear factor (NF)-κB, nuclear factor of activated T cell, and activating protein-1 pathways, and directly inhibited B cells by blocking Bruton's tyrosine kinase (BTK) signaling and the downstream NF-κB and Myc pathways. Overall, our results demonstrated that DHA inhibited Tfh cells by blocking ITK signaling and also directly inhibited B cells by blocking BTK signaling. Therefore, reducing the production of pathogenic antibodies might effectively treat SLE.© 2024. The Pharmaceutical Society of Korea.