Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2020; 11(6): 239-251
Published online Jun 15, 2020. doi: 10.4239/wjd.v11.i6.239
CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes
Jing Zhang, Su-Bee Tan, Zhi-Gang Guo
Jing Zhang, Zhi-Gang Guo, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210097, Jiangsu Province, China
Jing Zhang, Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States
Su-Bee Tan, National Key Laboratory for Biochemistry, College of Life Sciences, Nanjing University, Nanjing 210093, Jiangsu Province, China
Author contributions: Guo ZG and Zhang J conceived and designed the study; Zhang J and Tan SB performed the experiments and wrote the manuscript; Guo ZG and Tan SB revised the manuscript.
Supported by the National Natural Science Foundation of China, No. 31701179; the China Postdoctoral Science Foundation, No. 2016M591877.
Institutional animal care and use committee statement: The Institutional Animal Care and Use Committee of Nanjing Normal University provided approval for this study.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zhi-Gang Guo, PhD, Professor, Senior Research Fellow, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210097, Jiangsu Province, China. guozgang@gmail.com
Received: November 7, 2019
Peer-review started: November 7, 2019
First decision: December 12, 2019
Revised: March 30, 2020
Accepted: April 18, 2020
Article in press: April 18, 2020
Published online: June 15, 2020
Abstract
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.

Keywords: Type I diabetes, Immune defense, CD47, Migration, Phagocytosis, Cell-cell interaction

Core tip: Type I diabetes (T1D) has caused worldwide public health concerns. The mechanochemical regulation of the disease-induced immune response raised more considerations. We provide mechanistic insights into T1D, associating interactions between membrane structures and inflammatory disease progression. The immune response could be a novel section for preventing the T1D progression.