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
  • Zebrafish
  • Mice
  • Neutrophils*
  • Endoplasmic Reticulum Stress
  • Inflammation/metabolism
  • Mammals
  • Animals
  • Apoptosis
  • Macrophages/metabolism
  • Insulin-Secreting Cells*/metabolism
(all 10)
PubMed
36001973 Full text @ Cell Rep.
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
Figures
Figure Gallery (6 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
c264TgTransgenic Insertion
    gl22TgTransgenic Insertion
      gl24TgTransgenic Insertion
        nz50TgTransgenic Insertion
          nz117TgTransgenic Insertion
            pd1028TgTransgenic Insertion
              st95
                		Small Deletion
                vu513TgTransgenic Insertion
                  vu530TgTransgenic Insertion
                    xt6TgTransgenic Insertion
                      1 - 10 of 13
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      cxcl8aCRISPR2-cxcl8aCRISPR
                      cxcl8aCRISPR3-cxcl8aCRISPR
                      tnfaCRISPR13-tnfaCRISPR
                      tnfaCRISPR14-tnfaCRISPR
                      1 - 4 of 4
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                      Fish
                      No data available
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab1-inspolyclonalGuinea pig
                      1 - 1 of 1
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                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      DsRed2EFGDsRed2
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      GFPEFGGFP
                      LanYFPEFGLanYFP
                      mCherryEFGmCherry
                      NTREFGNTR
                      TomatoEFGTomato
                      1 - 8 of 8
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                      Mapping
                      No data available
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                      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.