Celastrol ameliorates lupus by promoting apoptosis of autoimmune T cells and preventing autoimmune response in MRL/lpr mice

IF 3.7 2区 医学 Q1 RHEUMATOLOGY Lupus Science & Medicine Pub Date : 2024-03-01 DOI:10.1136/lupus-2023-001057
Tianhong Xie, Hongliang Rui, Huiqiang Liu, Xin Liu, Xiang Liu, Ping Li
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Abstract

Objective Celastrol is a bioactive constituent extracted from Tripterygium wilfordii (thunder god vine). It has been demonstrated to have a therapeutic effect on experimental disease models for chronic inflammatory and immune disorders. In the present study, we investigated whether and how celastrol exerts a regulatory effect on the autoimmune response in MRL/lpr mice. Methods We performed an in vivo study to determine the therapeutic effects of celastrol in MRL/lpr mice and then further investigated the underlying mechanism of celastrol in the regulation of the autoimmune response in MRL/lpr mice. Results Celastrol showed a therapeutic effect in MRL/lpr mice by preventing the enlargement of the spleen and lymph nodes, alleviating renal injury, and reducing the levels of ANA and anti-double-stranded DNA antibodies. Furthermore, celastrol suppressed the in vivo inflammatory response in MRL/lpr mice by reducing the serum levels of multiple cytokines, including interleukin (IL)-6, tumour necrosis factor (TNF) and interferon (IFN)-γ, and the production of multiple antibody subsets, including total IgG, IgG1 and IgG2b. In vitro, celastrol reduced anti-CD3 antibody stimulation-induced T helper 1 and TNF-producing cells in CD4+ T cells of MRL/lpr mice. In addition, celastrol significantly affected B cell differentiation and prevented the generation of plasma cells from B cells in MRL/lpr mice by reducing the frequency of activated and germinal centre B cells. Celastrol treatment also affected T cell differentiation and significantly reduced central memory T cell frequencies in MRL/lpr mice. Importantly, celastrol treatment specifically promoted apoptosis of CD138+ but not CD138− T cells to suppress autoimmune T cell accumulation in MRL/lpr mice. Conclusions Celastrol exerted therapeutic effects on lupus by specifically promoting apoptosis of autoimmune T cells and preventing the progression of autoimmune response. Data are available upon reasonable request.
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Celastrol 通过促进自身免疫 T 细胞凋亡和预防 MRL/lpr 小鼠的自身免疫反应来改善狼疮症状
目的 Celastrol 是一种从雷公藤(Tripterygium wilfordii)中提取的生物活性成分。实验证明,它对慢性炎症和免疫性疾病的实验模型有治疗作用。在本研究中,我们探讨了青蒿素是否以及如何对 MRL/lpr 小鼠的自身免疫反应产生调节作用。方法 我们进行了一项体内研究,以确定青霉烯醇对 MRL/lpr 小鼠的治疗效果,然后进一步研究青霉烯醇调节 MRL/lpr 小鼠自身免疫反应的内在机制。结果 车前子醇对MRL/lpr小鼠有治疗作用,可防止脾脏和淋巴结肿大,减轻肾损伤,降低ANA和抗双链DNA抗体水平。此外,通过降低多种细胞因子(包括白细胞介素 (IL)-6、肿瘤坏死因子 (TNF) 和干扰素 (IFN)-γ)的血清水平以及多种抗体亚群(包括总 IgG、IgG1 和 IgG2b)的产生,青蒿素抑制了 MRL/lpr 小鼠体内的炎症反应。在体外,西司替醇减少了抗 CD3 抗体刺激诱导的 T 辅助细胞 1 和 MRL/lpr 小鼠 CD4+ T 细胞中的 TNF 生成细胞。此外,西司他洛尔还通过降低活化和生殖中心B细胞的频率,明显影响了MRL/lpr小鼠的B细胞分化,并阻止了B细胞生成浆细胞。西司他醇治疗也会影响T细胞分化,并显著降低MRL/lpr小鼠的中心记忆T细胞频率。重要的是,塞拉司醇治疗可特异性地促进 CD138+ T 细胞而非 CD138- T 细胞的凋亡,从而抑制 MRL/lpr 小鼠自身免疫 T 细胞的积累。结论 西司他醇通过特异性促进自身免疫T细胞凋亡和阻止自身免疫反应的进展,对狼疮产生治疗效果。如有合理要求,可提供相关数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Lupus Science & Medicine
Lupus Science & Medicine RHEUMATOLOGY-
CiteScore
5.30
自引率
7.70%
发文量
88
审稿时长
15 weeks
期刊介绍: Lupus Science & Medicine is a global, peer reviewed, open access online journal that provides a central point for publication of basic, clinical, translational, and epidemiological studies of all aspects of lupus and related diseases. It is the first lupus-specific open access journal in the world and was developed in response to the need for a barrier-free forum for publication of groundbreaking studies in lupus. The journal publishes research on lupus from fields including, but not limited to: rheumatology, dermatology, nephrology, immunology, pediatrics, cardiology, hepatology, pulmonology, obstetrics and gynecology, and psychiatry.
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