Volume 7, Issue 3 2200925
Research Article

Engineered Cell Membrane Vesicles Expressing CD40 Alleviate System Lupus Nephritis by Intervening B Cell Activation

Tianliang Fang

Tianliang Fang

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Baoqi Li

Baoqi Li

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Meng Li

Meng Li

Department of Dermatology, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China

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Yuli Zhang

Yuli Zhang

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Zhangyan Jing

Zhangyan Jing

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Yuan Li

Yuan Li

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Tianyuan Xue

Tianyuan Xue

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Zhirang Zhang

Zhirang Zhang

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Wenli Fang

Wenli Fang

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Zhongda Lin

Zhongda Lin

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Fanqiang Meng

Fanqiang Meng

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Liyan Li

Liyan Li

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Yang Yang

Yang Yang

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433 China

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Xingding Zhang

Xingding Zhang

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

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Xin Liang

Corresponding Author

Xin Liang

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Key Laboratory of Stem Cell and Regenerative Tissue Engineering, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808 China

E-mail: [email protected]

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Shu-Na Chen

Corresponding Author

Shu-Na Chen

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

E-mail: [email protected]

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Jun Chen

Corresponding Author

Jun Chen

Department of Dermatology, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China

E-mail: [email protected]

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Xudong Zhang

Corresponding Author

Xudong Zhang

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107 China

E-mail: [email protected]

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First published: 05 January 2023
Citations: 6

Abstract

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.

Conflict of Interest

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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