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CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes
BACKGROUND: Type I diabetes (T1D) is characterized by insulin loss caused by inflammatory cells that excessively infiltrate and destroy the pancreas, resulting in dysregulation of tissue homeostasis, mechanobiological properties, and the immune response. The streptozotocin (STZ)-induced mouse model...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284019/ https://www.ncbi.nlm.nih.gov/pubmed/32547698 http://dx.doi.org/10.4239/wjd.v11.i6.239 |
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author | Zhang, Jing Tan, Su-Bee Guo, Zhi-Gang |
author_facet | Zhang, Jing Tan, Su-Bee Guo, Zhi-Gang |
author_sort | Zhang, Jing |
collection | PubMed |
description | BACKGROUND: Type I diabetes (T1D) is characterized by insulin loss caused by inflammatory cells that excessively infiltrate and destroy the pancreas, resulting in dysregulation of tissue homeostasis, mechanobiological properties, and the immune response. The streptozotocin (STZ)-induced mouse model exhibits multiple features of human T1D and enables mechanistic analysis of disease progression. However, the relationship between the mechanochemical signaling regulation of STZ-induced T1D and macrophage migration and phagocytosis is unclear. AIM: To study the mechanochemical regulation of STZ-induced macrophage response on pancreatic beta islet cells to gain a clearer understanding of T1D. METHODS: We performed experiments using different methods. We stimulated isolated pancreatic beta islet cells with STZ and then tested the macrophage migration and phagocytosis. RESULTS: In this study, we discovered that the integrin-associated surface factor CD47 played a critical role in immune defense in the STZ-induced T1D model by preventing pancreatic beta islet inflammation. In comparison with healthy mice, STZ-treated mice showed decreased levels of CD47 on islet cells and reduced interaction of CD47 with signal regulatory protein α (SIRPα), which negatively regulates macrophage-mediated phagocytosis. This resulted in weakened islet cell immune defense and promoted macrophage migration and phagocytosis of target inflammatory cells. Moreover, lipopolysaccharide-activated human acute monocytic leukemia THP-1 cells also exhibited enhanced phagocytosis in the STZ-treated islets, and the aggressive attack of the inflammatory islets correlated with impaired CD47-SIRPα interactions. In addition, CD47 overexpression rescued the pre-labeled targeted cells. CONCLUSION: This study indicates that CD47 deficiency promotes the migration and phagocytosis of macrophages and provides mechanistic insights into T1D by associating the interactions between membrane structures and inflammatory disease progression. |
format | Online Article Text |
id | pubmed-7284019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-72840192020-06-15 CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes Zhang, Jing Tan, Su-Bee Guo, Zhi-Gang World J Diabetes Basic Study BACKGROUND: Type I diabetes (T1D) is characterized by insulin loss caused by inflammatory cells that excessively infiltrate and destroy the pancreas, resulting in dysregulation of tissue homeostasis, mechanobiological properties, and the immune response. The streptozotocin (STZ)-induced mouse model exhibits multiple features of human T1D and enables mechanistic analysis of disease progression. However, the relationship between the mechanochemical signaling regulation of STZ-induced T1D and macrophage migration and phagocytosis is unclear. AIM: To study the mechanochemical regulation of STZ-induced macrophage response on pancreatic beta islet cells to gain a clearer understanding of T1D. METHODS: We performed experiments using different methods. We stimulated isolated pancreatic beta islet cells with STZ and then tested the macrophage migration and phagocytosis. RESULTS: In this study, we discovered that the integrin-associated surface factor CD47 played a critical role in immune defense in the STZ-induced T1D model by preventing pancreatic beta islet inflammation. In comparison with healthy mice, STZ-treated mice showed decreased levels of CD47 on islet cells and reduced interaction of CD47 with signal regulatory protein α (SIRPα), which negatively regulates macrophage-mediated phagocytosis. This resulted in weakened islet cell immune defense and promoted macrophage migration and phagocytosis of target inflammatory cells. Moreover, lipopolysaccharide-activated human acute monocytic leukemia THP-1 cells also exhibited enhanced phagocytosis in the STZ-treated islets, and the aggressive attack of the inflammatory islets correlated with impaired CD47-SIRPα interactions. In addition, CD47 overexpression rescued the pre-labeled targeted cells. CONCLUSION: This study indicates that CD47 deficiency promotes the migration and phagocytosis of macrophages and provides mechanistic insights into T1D by associating the interactions between membrane structures and inflammatory disease progression. Baishideng Publishing Group Inc 2020-06-15 2020-06-15 /pmc/articles/PMC7284019/ /pubmed/32547698 http://dx.doi.org/10.4239/wjd.v11.i6.239 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Basic Study Zhang, Jing Tan, Su-Bee Guo, Zhi-Gang CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes |
title | CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes |
title_full | CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes |
title_fullStr | CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes |
title_full_unstemmed | CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes |
title_short | CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes |
title_sort | cd47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type i diabetes |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284019/ https://www.ncbi.nlm.nih.gov/pubmed/32547698 http://dx.doi.org/10.4239/wjd.v11.i6.239 |
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