PD-L1 cellular nanovesicles carrying rapamycin inhibit alloimmune responses in transplantation
| Autor: | Gang Zheng, Xiaowei Xu, Fuxia Yan, Gan Liu, Min Yang, Weiwei Zeng, Jianhua Feng, Hualian Zha, Lifang Xi, Yingyi Wu, Zhanxue Xu, Qiumei Lu, Yan Hailan, Fang Cheng, Hongbo Chen, He Chao, Yunzhi Ling, Dandan Su, Hsiang-I Tsai |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Graft Rejection
medicine.medical_specialty Programmed Cell Death 1 Receptor Cell Biomedical Engineering Lymphocyte Activation B7-H1 Antigen Organ transplantation Mice 03 medical and health sciences 0302 clinical medicine Immune system PD-L1 medicine Animals General Materials Science PI3K/AKT/mTOR pathway 030304 developmental biology Sirolimus 0303 health sciences biology business.industry Immune checkpoint Transplantation medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Cancer research business |
| Zdroj: | Biomaterials Science. 9:1246-1255 |
| ISSN: | 2047-4849 2047-4830 |
| DOI: | 10.1039/d0bm01798a |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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