journal article·2020-07

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, Zhen Gu

Advanced Materials· Volume 32· Issue 26
Publisher page

Abstract

Abstract 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.
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Research context

OpenAlex topics: Diabetes and associated disorders · Pancreatic function and diabetes · Diabetes Management and Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Bioengineering University of California Los Angeles CA 90095 USA

California NanoSystems Institute University of California Los Angeles CA 90095 USA

Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University Raleigh NC 27695 USA

Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon‐Based Functional Materials and Devices Soochow University Suzhou 215123 P. R. China

Department of Materials Science and Engineering Drexel University Philadelphia PA 19104 USA

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging School of Biomedical Engineering, Health Science Center Shenzhen University Shenzhen 518060 China

Jonsson Comprehensive Cancer Center University of California Los Angeles CA 90095 USA

Center for Minimally Invasive Therapeutics University of California Los Angeles CA 90095 USA

Funding

Alfred P. Sloan Foundation · North Carolina State University · National Natural Science Foundation of China

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