Research
| Title： | Macrophages and neutrophils are necessary for ER stress-induced beta cell loss |
|---|---|
| First author： | Yang, Bingyuan; Yang, Liu; Wang, Yueyang; Maddison, Lisette A.; Tang, Zihan; Haigh, Sander; Gong, Yulong; Zhang, Yue; Covington, Brittney A.; Bosma, Karin J.; Tong, Xin; Page-McCaw, Patrick; Gannon, Maureen; Deng, Qing; Chen, Wenbiao |
| Journal： | CELL REPORTS |
| Years： | 2022 |
| DOI： | 10.1016/j.celrep.2022.111255 |
| Abstract： | Persistent endoplasmic reticulum (ER) stress induces islet inflammation and beta cell loss. How islet inflamma-tion contributes to beta cell loss remains uncertain. We have reported previously that chronic overnutrition-induced ER stress in beta cells causes Ripk3-mediated islet inflammation, macrophage recruitment, and a reduction of beta cell numbers in a zebrafish model. We show here that beta cell loss results from the intricate com-munications among beta cells, macrophages, and neutrophils. Macrophage-derived Tnfa induces cxcl8a in beta cells. Cxcl8a, in turn, attracts neutrophils to macrophage-contacted hotspotswhere beta cell loss occurs. We also show potentiation of chemokine expression in stressed mammalian beta cells by macrophage-derived TNFA. In Akita and db/db mice, there is an increase in CXCL15-positive beta cells and intra-islet neutrophils. Blocking neutrophil recruitment in Akita mice preserves beta cell mass and slows diabetes progression. These results reveal an important role of neutrophils in persistent ER stress-induced beta cell loss. |
