Bioengineered Artificial Extracellular Vesicles Presenting PD-L1 and Gal-9 Ameliorate New-Onset Type 1 Diabetes.
Autor: | Yang Z; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Zhang Z; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Li L; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Jing Z; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Ma Y; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Lan T; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Li Y; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Lin Z; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Fang W; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Zhang J; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China., Zhang J; Department of Gynaecology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, China., Liang X; 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, Guangdong, China., Wu B; Center for Medical Experiments (CME), Benqing Laboratory, Guangming District People's Hospital, Shenzhen, Guangdong, China., Zheng Y; Center for Medical Experiments (CME), Benqing Laboratory, Guangming District People's Hospital, Shenzhen, Guangdong, China., Zhang X; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China. |
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Jazyk: | angličtina |
Zdroj: | Diabetes [Diabetes] 2024 Aug 01; Vol. 73 (8), pp. 1325-1335. |
DOI: | 10.2337/db23-0987 |
Abstrakt: | An important factor in the development of type 1 diabetes (T1D) is the deficiency of inhibitory immune checkpoint ligands, specifically programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9), in β-cells. Therefore, modulation of pancreas-infiltrated T lymphocytes by exogenous PD-L1 or Gal-9 is an ideal approach for treating new-onset T1D. We genetically engineered macrophage cells to generate artificial extracellular vesicles (aEVs) overexpressing PD-L1 and Gal-9, which could restrict islet autoreactive T lymphocytes and protect β-cells from destruction. Intriguingly, overexpression of Gal-9 stimulated macrophage polarization to the M2 phenotype with immunosuppressive attributes. Alternatively, both PD-L1- and Gal-9-presenting aEVs (PD-L1-Gal-9 aEVs) favorably adhered to T cells via the interaction of programmed cell death protein 1/PD-L1 or T-cell immunoglobulin mucin 3/Gal-9. Moreover, PD-L1-Gal-9 aEVs prominently promoted effector T-cell apoptosis and splenic regulatory T (Treg) cell formation in vitro. Notably, PD-L1-Gal-9 aEVs efficaciously reversed new-onset hyperglycemia in NOD mice, prevented T1D progression, and decreased the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas, which together contributed to the preservation of residual β-cell survival and mitigation of hyperglycemia. (© 2024 by the American Diabetes Association.) |
Databáze: | MEDLINE |
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