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首页> 外文期刊>Biochemical Pharmacology >Paeoniflorin ameliorates murine lupus nephritis by increasing CD4(+)Foxp3(+) Treg cells via enhancing mTNF alpha-TNFR2 pathway
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Paeoniflorin ameliorates murine lupus nephritis by increasing CD4(+)Foxp3(+) Treg cells via enhancing mTNF alpha-TNFR2 pathway

机译：Paeoniflorin通过增强MTNFα-TNFR2途径增加CD4（+）Foxp3（+）Treg细胞来改善鼠狼疮性肾炎

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摘要

Treg cells are essential for re-establishing self-tolerance in lupus. However, given that direct Treg therapies may be inadequate to control autoimmunity and inflammation, a strategy of inducing or expanding endogenous Treg cells in vivo may be a good option. Macrophages are main tissue-infiltrating cells and play a role in promoting Treg differentiation while paeoniflorin (PF), a monoterpene glycoside, exhibits anti-inflammatory and immunoregulatory effects. Here, we studied the effects of PF on CD4+FoxP3+ Treg frequency and the potential mechanisms involving M2 macrophages. We demonstrated that PF ameliorated lupus nephritis in lupus-prone B6/gld mice by reducing urinary protein, serum creatinine and anti-dsDNA levels, diminishing renal cellular infiltration, improving renal immunopathology and downregulating renal gene and protein expressions of key cytokines, including IFN-?, IL-6, IL-12 and IL-23. PF also lowered the percentage of CD44highCD62Llow effector T cells while augmenting CD4+FoxP3+ Treg frequency in B6/gld mice. Importantly, PF increased TNFR2 expression on CD4+FoxP3+ Tregs, but not CD4+FoxP3- T cells, in vivo and in vitro. Furthermore, we found that CD206+ subset of F4/80+CD11b+ macrophages expressed a higher level of mTNF-? than their CD206- counterparts while PF increased mTNF-? expression on CD206+ macrophages in vitro and in vivo. In vitro studies showed that mTNF-?+ M2 macrophages were more potent in inducing Treg differentiation and proliferation than their mTNF?- counterparts, whereas the effects of mTNF-?+ M2 macrophages were largely reversed by separation of M2 macrophages using a transwell or TNFR2-blocking Ab in the culture. Finally, PF also promoted in vitro Treg generation induced by M2 macrophages. Thus, we demonstrated that mTNF?-TNFR2 interaction is a new mechanism responsible for Treg differentiation mediated by M2 macrophages. We provided the first evidence that PF may be used to treat lupus nephritis.
机译：Treg细胞对于重新建立狼疮的自我耐受性是必不可少的。然而，鉴于直接Treg疗法可能不充分以控制自身免疫和炎症，诱导或扩增体内内源性Treg细胞的策略可能是一个好的选择。巨噬细胞是主要的组织渗透细胞，并在促进Treg分化时发挥作用，而PaeoNiflorin（PF），一种单萜糖苷，含有抗炎和免疫调节作用。在这里，我们研究了PF对CD4 + Foxp3 + Treg频率的影响以及涉及M2巨噬细胞的潜在机制。我们证明，通过减少尿蛋白，血清肌酐和抗DSDNA水平，降低肾细胞浸润，改善肾免疫病理学和下调肾基因以及关键细胞因子的蛋白表达，包括IFN - ？，IL-6，IL-12和IL-23。 PF还降低了CD44highcd62llow效应器T细胞的百分比，同时在B6 / GLD小鼠中增强CD4 + Foxp3 + Treg频率。重要的是，PF在CD4 + Foxp3 + Tregs上增加TNFR2表达，但不是CD4 + FoxP3-T细胞，体内和体外。此外，我们发现CD206 + F4 / 80 + CD11B +巨噬细胞的子集表达了更高水平的MTNF-？比他们的CD206-对应物，而PF增加MTNF-？在体外和体内CD206 +巨噬细胞的表达。体外研究表明，MTNF - + M2巨噬细胞比其MTNFα-对应物诱导Treg分化和增殖更有效，而MTNF - α+ M2巨噬细胞的效果主要通过使用Transwell或TNFR2分离M2巨噬细胞来逆转M2巨噬细胞 - 在文化中吹嘘ab。最后，PF还促进了M2巨噬细胞诱导的体外Treg代。因此，我们证明MTNFα-TNFR2相互作用是负责由M2巨噬细胞介导的Treg分化的新机制。我们提供了PF可用于治疗狼疮性肾炎的第一种证据。

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  • 来源
    《Biochemical Pharmacology》 |2021年第1期|共13页
  • 作者

    Liang Chun-Ling; Lu Weihui; Qiu Feifei; Li Dan; Liu Huazhen; Zheng Fang; Zhang Qunfang; Chen Yuchao; Lu Chuanjian; Li Bin; Dai Zhenhua;

  • 作者单位

    Guangdong Prov Acad Chinese Med Sci Sect Immunol 55 Nei Huan Xi Lu Guangzhou 510006 Guangdong;

    Guangdong Prov Acad Chinese Med Sci Sect Immunol 55 Nei Huan Xi Lu Guangzhou 510006 Guangdong;

    Guangdong Prov Acad Chinese Med Sci Sect Immunol 55 Nei Huan Xi Lu Guangzhou 510006 Guangdong;

    Shanghai Jiao Tong Univ Shanghai Inst Immunol Dept Immunol Sch Med Shanghai 200025 Peoples R;

    Guangdong Prov Acad Chinese Med Sci Sect Immunol 55 Nei Huan Xi Lu Guangzhou 510006 Guangdong;

    Guangdong Prov Acad Chinese Med Sci Sect Immunol 55 Nei Huan Xi Lu Guangzhou 510006 Guangdong;

    Guangdong Prov Acad Chinese Med Sci Sect Immunol 55 Nei Huan Xi Lu Guangzhou 510006 Guangdong;

    Guangdong Prov Acad Chinese Med Sci Sect Immunol 55 Nei Huan Xi Lu Guangzhou 510006 Guangdong;

    Guangdong Prov Acad Chinese Med Sci Sect Immunol 55 Nei Huan Xi Lu Guangzhou 510006 Guangdong;

    Shanghai Jiao Tong Univ Shanghai Inst Immunol Dept Immunol Sch Med Shanghai 200025 Peoples R;

    Guangdong Prov Acad Chinese Med Sci Sect Immunol 55 Nei Huan Xi Lu Guangzhou 510006 Guangdong;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

    Lupus nephritis; Paeoniflorin; Macrophage; TNF-?; TNFR2; Treg;

    机译：狼疮肾炎;芍药蛋白;巨噬细胞;tnf - ?;tnfr2;treg;

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