Journal article
Engineered PD-L1-Expressing Platelets Reverse New-Onset Type 1 Diabetes
Advanced materials (Weinheim), v 32(26), pp e1907692-n/a
Jul 2020
PMID: 32449212
Featured in Collection : UN Sustainable Development Goals @ Drexel
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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Details
- Title
- Engineered PD-L1-Expressing Platelets Reverse New-Onset Type 1 Diabetes
- Creators
- Xudong Zhang - University of California, Los AngelesYang Kang - University of California, Los AngelesJinqiang Wang - University of California, Los AngelesJunjie Yan - Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USAQian Chen - University of California, Los AngelesHao Cheng - Drexel UniversityPeng Huang - Shenzhen University Health Science CenterZhen Gu - University of California, Los Angeles
- Publication Details
- Advanced materials (Weinheim), v 32(26), pp e1907692-n/a
- Publisher
- Wiley
- Grant note
- 2020A1515011443 / Guangdong Basic and Applied Basic Research Foundation 2018B030308003 / Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project 51703132 / National Natural Science Foundation of China 2019A1515010855 / Guangdong Basic and Applied Basic Research Foundation 51728301 / National Natural Science Foundation of China 51573096 / National Natural Science Foundation of China 31771036 / National Natural Science Foundation of China 161032 / Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China JCYJ20170412111100742 / Basic Research Program of Shenzhen Alfred P. Sloan Foundation JCYJ20160422091238319 / Basic Research Program of Shenzhen 1-PNF-2018-658-A-N / NC State University 31971268 / National Natural Science Foundation of China
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Materials Science and Engineering
- Web of Science ID
- WOS:000535016800001
- Scopus ID
- 2-s2.0-85085618035
- Other Identifier
- 991019169103304721
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- 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