PD-L1 cellular nanovesicles carrying rapamycin inhibit alloimmune responses in transplantation

Min Yang; Zhanxue Xu; Hailan Yan; Hsiang-I Tsai; Dandan Su; Fuxia Yan; Qiumei Lu; Jianhua Feng; Weiwei Zeng; Lifang Xi; Hualian Zha; Yunzhi Ling; Chao He; Yingyi Wu; Xiaowei Xu; Gang Zheng; Gan Liu; Hongbo Chen; Fang Cheng

doi:10.1039/d0bm01798a

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PD-L1 cellular nanovesicles carrying rapamycin inhibit alloimmune responses in transplantation

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PD-L1 cellular nanovesicles carrying rapamycin inhibit alloimmune responses in transplantation

Min Yang, Zhanxue Xu, Hailan Yan, Hsiang-I Tsai, Dandan Su, Fuxia Yan, Qiumei Lu, Jianhua Feng, Weiwei Zeng, Lifang Xi, …

Biomaterials science, Vol.9(4), pp.1246-1255

23/02/2021

DOI: https://doi.org/10.1039/d0bm01798a

PMID: 33367372

Résumé

Animals

B7-H1 Antigen

Graft Rejection - prevention & control

Lymphocyte Activation

Mice

Programmed Cell Death 1 Receptor

Sirolimus - pharmacology

Organ transplantation has been employed upon serious injuries, but a T-cell-mediated potent inflammatory immune response often leads to graft rejection. Immunosuppressive drugs such as rapamycin (RAPA) have to be taken after organ transplantation, but long-term use of these drugs causes severe adverse effects. Immune checkpoint pathways such as the programmed death-receptor 1/programmed death-ligand 1 (PD-1/PD-L1) provides an immunosuppressive environment, preventing excessive tissue destruction due to inflammatory immune responses. In this study, we bioengineered cell membrane-derived PD-L1 nanovesicles (PD-L1 NVs) to carry low doses of RAPA. These NVs inhibited T-cell activation and proliferation in vitro, by enhancing the PD-1/PD-L1 immune co-inhibitory signaling axis and inhibiting the mTOR pathway. Importantly, PD-L1 NVs encapsulated with rapamycin exerted stronger effects on inhibiting T-cell proliferation than PD-L1 NVs or rapamycin alone. This can be recapitulated in a mouse skin transplantation model, leading to the weakened alloimmune response and allograft tolerance. We also found that PD-L1/rapamycin vesicles have additional function to induce regulatory T cells in the recipient spleens. Our study highlighted the power of combining low-dose rapamycin and PD-L1 in the nanovesicles as immunosuppressants to promote allograft acceptance.

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Titre: PD-L1 cellular nanovesicles carrying rapamycin inhibit alloimmune responses in transplantation
Créateurs - sans rôle: Min Yang - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Zhanxue Xu - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Hailan Yan - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Hsiang-I Tsai - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Dandan Su - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Fuxia Yan - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Qiumei Lu - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Jianhua Feng - Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
Weiwei Zeng - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Lifang Xi - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Hualian Zha - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Yunzhi Ling - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Chao He - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Yingyi Wu - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Xiaowei Xu - Clinical Neuroscience Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518000, China
Gang Zheng - XuZhou Central Hospital Affiliated to Medical School of Southeast University, XuZhou, 221000, China
Gan Liu - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Hongbo Chen - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Fang Cheng - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China. chengf9@mail.sysu.edu.cn chenhb7@mail.sysu.edu.cn liugan5@mail.sysu.edu.cn
Détails de publication: Biomaterials science, Vol.9(4), pp.1246-1255
Identifiants: 99139026409311
Unité académique: Institut Européen des Membranes - IEM
Langue: English
Type de ressource: Journal article