PUBLICATION
Macrophages and neutrophils are necessary for ER stress-induced β cell loss
- Authors
- Yang, B., Yang, L., Wang, Y., Maddison, L.A., Tang, Z., Haigh, S., Gong, Y., Zhang, Y., Covington, B.A., Bosma, K.J., Tong, X., Page-McCaw, P., Gannon, M., Deng, Q., Chen, W.
- ID
- ZDB-PUB-220825-4
- Date
- 2022
- Source
- Cell Reports 40: 111255 (Journal)
- Registered Authors
- Chen, Wenbiao
- Keywords
- CP, ER stress, Metabolism, diabetes, islet inflammation, macrophages, neutrophils, overnutrition, zebrafish, β cell loss
- MeSH Terms
-
- Animals
- Apoptosis
- Endoplasmic Reticulum Stress
- Inflammation/metabolism
- Insulin-Secreting Cells*/metabolism
- Macrophages/metabolism
- Mammals
- Mice
- Neutrophils*
- Zebrafish
- PubMed
- 36001973 Full text @ Cell Rep.
Citation
Yang, B., Yang, L., Wang, Y., Maddison, L.A., Tang, Z., Haigh, S., Gong, Y., Zhang, Y., Covington, B.A., Bosma, K.J., Tong, X., Page-McCaw, P., Gannon, M., Deng, Q., Chen, W. (2022) Macrophages and neutrophils are necessary for ER stress-induced β cell loss. Cell Reports. 40:111255.
Abstract
Persistent endoplasmic reticulum (ER) stress induces islet inflammation and β cell loss. How islet inflammation contributes to β cell loss remains uncertain. We have reported previously that chronic overnutrition-induced ER stress in β cells causes Ripk3-mediated islet inflammation, macrophage recruitment, and a reduction of β cell numbers in a zebrafish model. We show here that β cell loss results from the intricate communications among β cells, macrophages, and neutrophils. Macrophage-derived Tnfa induces cxcl8a in β cells. Cxcl8a, in turn, attracts neutrophils to macrophage-contacted "hotspots" where β cell loss occurs. We also show potentiation of chemokine expression in stressed mammalian β cells by macrophage-derived TNFA. In Akita and db/db mice, there is an increase in CXCL15-positive β cells and intra-islet neutrophils. Blocking neutrophil recruitment in Akita mice preserves β cell mass and slows diabetes progression. These results reveal an important role of neutrophils in persistent ER stress-induced β cell loss.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping