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狼疮合剂通过防止MRL/lpr小鼠中CD138+ T细胞的积累来改善狼疮。

LangChuangHeJi decoction ameliorates lupus via preventing accumulation of CD138+ T cells in MRL/lpr mice.

作者信息

Xie Tianhong, Liu Xin, Liu Huiqiang, Han Xuyang, Zhao Jingxia, Zhou Dongmei, Wang Yan, Zhang Hongkai, Wang Ping, Li Ping

机构信息

Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine Beijing 100010, China.

Department of Pathology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University Beijing 100010, China.

出版信息

Am J Transl Res. 2021 Nov 15;13(11):12440-12460. eCollection 2021.

Abstract

LangChuangHeJi (LCHJ) decoction has been used as a supplementary therapy to reduce the dose of prednisone and improve the therapeutic effects in systemic lupus erythematosus (SLE) maintenance. We aimed to explore the underlying mechanisms of the therapeutic effects of LCHJ. Spleen and lymph node weight, renal tissue histology, anti-dsDNA and anti-nuclear antibody levels in serum, and urinary protein levels were measured to evaluate the therapeutic effects. We further measured serum levels of multiple cytokines and antibody subsets, and performed flow cytometry analysis to observe effects of LCHJ on the frequency and activation of T cells and T cell subsets, as well as accumulation of plasma cells in splenocytes of MRL/lpr mice. LCHJ exhibited significant therapeutic effects on MRL/lpr mice. LCHJ significantly controlled the in vivo inflammation and dramatically prevented the accumulation of DN T and plasma cells in MRL/lpr mice. Moreover, LCHJ significantly suppressed the accumulation of CD138+ T cells in MRL/lpr mice, which led to the decreased production of the anti-dsDNA antibody in vivo. LCHJ significantly decreased CD4+CD138+ T cells originated from CD4+CD138- T cells, which subsequently prevented the accumulation of CD138+ T cells in MRL/lpr mice. Our results indicated that LCHJ alleviated renal injuries and prevented the enlargement of the spleen and lymph nodes by suppressing DN T cell accumulation, and reduced anti-dsDNA antibody secretion by preventing the accumulation of CD138+ T cells.

摘要

狼疮合剂(LCHJ)已被用作辅助疗法,以减少泼尼松的剂量并提高系统性红斑狼疮(SLE)维持期的治疗效果。我们旨在探讨LCHJ治疗效果的潜在机制。测量脾脏和淋巴结重量、肾组织组织学、血清中抗双链DNA和抗核抗体水平以及尿蛋白水平,以评估治疗效果。我们进一步测量了多种细胞因子和抗体亚群的血清水平,并进行了流式细胞术分析,以观察LCHJ对MRL/lpr小鼠T细胞及其亚群的频率和活化以及脾细胞中浆细胞积累的影响。LCHJ对MRL/lpr小鼠表现出显著的治疗效果。LCHJ显著控制了体内炎症,并显著阻止了MRL/lpr小鼠中双阴性T细胞(DN T)和浆细胞的积累。此外,LCHJ显著抑制了MRL/lpr小鼠中CD138⁺ T细胞的积累,这导致体内抗双链DNA抗体的产生减少。LCHJ显著降低了源自CD4⁺CD138⁻ T细胞的CD4⁺CD138⁺ T细胞,从而阻止了MRL/lpr小鼠中CD138⁺ T细胞的积累。我们的结果表明,LCHJ通过抑制DN T细胞积累减轻了肾损伤并防止了脾脏和淋巴结肿大,并通过阻止CD138⁺ T细胞积累减少了抗双链DNA抗体的分泌。

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Treatment targets in SLE: remission and low disease activity state.SLE 的治疗目标:缓解和低疾病活动度状态。
Rheumatology (Oxford). 2020 Dec 5;59(Suppl5):v19-v28. doi: 10.1093/rheumatology/keaa420.
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Update on Lupus Nephritis: Core Curriculum 2020.狼疮肾炎更新:2020 年核心课程。
Am J Kidney Dis. 2020 Aug;76(2):265-281. doi: 10.1053/j.ajkd.2019.10.017. Epub 2020 Mar 24.
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Novel paradigms in systemic lupus erythematosus.系统性红斑狼疮的新范式。
Lancet. 2019 Jun 8;393(10188):2344-2358. doi: 10.1016/S0140-6736(19)30546-X. Epub 2019 Jun 6.

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