CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes
CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes
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胰岛细胞 CD47 下降促进 I 型糖尿病巨噬细胞介导的吞噬作用
DOI：
10.4239/wjd.v11.i6.239
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发表时间：
2020-06
影响因子：
4.2
通讯作者：
Zhi-Gang Guo
中科院分区：
文献类型：
--
作者：
Jing Zhang;Su-Bee Tan;Zhi-Gang Guo
背景I型糖尿病（T1 D）的特征在于由过度浸润和破坏胰腺的炎性细胞引起的胰岛素损失，导致组织稳态、机械生物学特性和免疫应答的失调。链脲佐菌素（STZ）诱导的小鼠模型表现出人类T1 D的多种特征，并能够对疾病进展进行机制分析。然而，STZ诱导的T1 D的机械化学信号调节与巨噬细胞迁移和吞噬作用之间的关系尚不清楚。目的研究链脲佐菌素（STZ）诱导的巨噬细胞对胰岛β细胞反应的机械化学调控，以更好地了解T1 D。方法采用不同方法进行实验。我们用STZ刺激分离的胰岛β细胞，然后测试巨噬细胞的迁移和吞噬作用。结果在本研究中，我们发现整合素相关表面因子CD 47通过防止胰岛β细胞炎症在STZ诱导的T1 D模型中的免疫防御中发挥关键作用。与健康小鼠相比，STZ处理的小鼠显示胰岛细胞上的CD 47水平降低，CD 47与信号调节蛋白α（SIRPα）的相互作用降低，SIRP α负调节巨噬细胞介导的吞噬作用。这导致胰岛细胞免疫防御减弱，并促进巨噬细胞迁移和对靶炎症细胞的吞噬。此外，脂多糖激活的人急性单核细胞白血病THP-1细胞在STZ处理的胰岛中也表现出增强的吞噬作用，并且炎症性胰岛的侵袭性攻击与受损的CD 47-SIRPα相互作用相关。此外，CD 47过表达拯救了预先标记的靶细胞。结论CD 47缺陷可促进巨噬细胞的迁移和吞噬功能，并通过膜结构与炎症性疾病进展之间的相互作用为T1 D的发病机制提供了新的认识。
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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影响因子：
5.8
作者：
Soto-Pantoja DR;Stein EV;Rogers NM;Sharifi-Sanjani M;Isenberg JS;Roberts DD
通讯作者：
Roberts DD
影响因子：
32.4
作者：
Yi T;Li J;Chen H;Wu J;An J;Xu Y;Hu Y;Lowell CA;Cyster JG
通讯作者：
Cyster JG
影响因子：
11.2
作者：
Chao MP;Alizadeh AA;Tang C;Jan M;Weissman-Tsukamoto R;Zhao F;Park CY;Weissman IL;Majeti R
通讯作者：
Majeti R
影响因子：
3
作者：
O. Catanzaro;D. Dziubecki;E. Labal;P. Sirois
通讯作者：
O. Catanzaro;D. Dziubecki;E. Labal;P. Sirois
影响因子：
3.1
作者：
Geunes-Boyer, Scarlett;Oliver, Timothy N.;Wright, Jo Rae
通讯作者：
Wright, Jo Rae