| First Author | Yang B | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 8 | Pages | 111255 |
| PubMed ID | 36001973 | Mgi Jnum | J:328274 |
| Mgi Id | MGI:7334653 | Doi | 10.1016/j.celrep.2022.111255 |
| Citation | Yang B, et al. (2022) Macrophages and neutrophils are necessary for ER stress-induced beta cell loss. Cell Rep 40(8):111255 |
| abstractText | Persistent endoplasmic reticulum (ER) stress induces islet inflammation and beta cell loss. How islet inflammation 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 communications among beta cells, macrophages, and neutrophils. Macrophage-derived Tnfa induces cxcl8a in beta cells. Cxcl8a, in turn, attracts neutrophils to macrophage-contacted "hotspots" where 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. |
