Engineered Cell Membrane Vesicles Expressing CD40 Alleviate System Lupus Nephritis by Intervening B Cell Activation
Engineered Cell Membrane Vesicles Expressing CD40 Alleviate System Lupus Nephritis by Intervening B Cell Activation
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DOI：
10.1002/smtd.202200925
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发表时间：
2023-01-05
期刊：
影响因子：
12.4
通讯作者：
Zhang, Xudong
中科院分区：
文献类型：
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作者：
Fang, Tianliang;Li, Baoqi;Zhang, Xudong
免疫干预B细胞激活以阻断自身抗体的产生引起了系统性红斑狼疮(SLE)治疗发展领域的浓厚兴趣。尽管SLE的存活率有所提高，但许多患者过早死亡。工程细胞膜囊泡具有显著的靶向给药和免疫调节能力，如B细胞。在这里，这项工作工程细胞纳米囊泡(NV)提供CD40(CD40NV)，可以钝化B细胞，从而减轻SLE。CD40NV通过阻断CD40L对CD4(+)T细胞的作用，破坏CD40/CD40L共刺激信号轴。因此，CD40NV抑制生发中心结构的产生和B细胞抗体的产生。此外，免疫抑制药物霉酚酸酯(MMF)也被包裹在囊泡(MMF-CD40Nvs)中，用于耗尽包括B细胞、T细胞和树突状细胞在内的免疫细胞。总之，CD40NV是缓解MRL/LPR小鼠自身免疫和狼疮性肾炎的有前景的制剂。
Immune intervention of B cell activation to blockade the production of autoantibodies provokes intense interest in the field of systemic lupus erythematosus (SLE) therapy development. Although the survival rate for SLE is improved, many patients die untimely. Engineered cell membrane vesicles manifest remarkable capacity of targeted drug delivery and immunomodulation of immune cells such as B cells. Herein, this work engineered cellular nanovesicles (NVs) presenting CD40 (CD40 NVs) that can blunt B cells and thus alleviate SLE. CD40 NVs disrupt the CD40/CD40 ligand (CD40L) costimulatory signal axis through the blockade of CD40L on CD4(+) T cells. Therefore, the CD40 NVs restrain the generation of the germinal center structure and production of antibodies from B cells. Furthermore, immunosuppressive drug mycophenolate mofetil (MMF) is also encapsulated in the vesicles (MMF-CD40 NVs), which is employed to deplete immunocytes including B cells, T cells, and dendritic cells. Together, CD40 NVs are promising formulations for relieving autoimmunity and lupus nephritis in MRL/lpr mice.