Logo image
Engineered PD-L1-Expressing Platelets Reverse New-Onset Type 1 Diabetes
Journal article   Peer reviewed

Engineered PD-L1-Expressing Platelets Reverse New-Onset Type 1 Diabetes

Xudong Zhang, Yang Kang, Jinqiang Wang, Junjie Yan, Qian Chen, Hao Cheng, Peng Huang and Zhen Gu
Advanced materials (Weinheim), v 32(26), pp e1907692-n/a
Jul 2020
PMID: 32449212

Abstract

Animals B7-H1 Antigen - genetics B7-H1 Antigen - metabolism Blood Glucose - analysis CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Diabetes Mellitus, Type 1 - pathology Diabetes Mellitus, Type 1 - therapy Diabetes Mellitus, Type 1 - veterinary Genetic Engineering Immune Tolerance Insulin - blood Insulin-Secreting Cells - cytology Insulin-Secreting Cells - immunology Insulin-Secreting Cells - metabolism Megakaryocyte Progenitor Cells - cytology Megakaryocyte Progenitor Cells - metabolism Megakaryocyte Progenitor Cells - transplantation Mice Mice, Inbred NOD T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism
The pathogenesis of Type 1 diabetes (T1D) arises from the destruction of insulin-producing β-cells by islet-specific autoreactive T cells. Inhibition of islet-specific autoreactive T cells to rescue β-cells is a promising approach to treat new-onset T1D. The immune checkpoint signal axis programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) can effectively regulate the activity of T cells and prevent autoimmune attack. Here, megakaryocyte progenitor cells are genetically engineered to overexpress PD-L1 to produce immunosuppressive platelets. The PD-L1-overexpressing platelets (designated PD-L1 platelets) accumulate in the inflamed pancreas and may suppress the activity of pancreas autoreactive T cells in newly hyperglycemic non-obese diabetic (NOD) mice, protecting the insulin-producing β-cells from destruction. Moreover, PD-L1 platelet treatment also increases the percentage of the regulatory T cells (Tregs) and maintains immune tolerance in the pancreas. It is demonstrated that the rescue of β-cells by PD-L1 platelets can effectively maintain normoglycemia and reverse diabetes in newly hyperglycemic NOD mice.

Metrics

23 Record Views
74 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Chemistry, Multidisciplinary
Chemistry, Physical
Materials Science, Multidisciplinary
Nanoscience & Nanotechnology
Physics, Applied
Physics, Condensed Matter
Logo image