AI Article Synopsis
- Type I diabetes (T1D) is marked by the destruction of insulin-producing pancreatic beta cells due to inflammation, and the study used a mouse model to explore its mechanisms.
- The research focused on how a surface protein called CD47 affects macrophage behavior and immune responses in T1D, revealing that lower CD47 levels lead to increased macrophage migration and phagocytosis of pancreatic cells.
- Findings suggest that enhancing CD47 expression could potentially improve immune defenses in the pancreas, providing new insights into the pathology of T1D.
Article 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284019 | PMC |
| http://dx.doi.org/10.4239/wjd.v11.i6.239 | DOI Listing |
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