Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes
Summary: Coordinated communication among pancreatic islet cells is necessary for maintenance of glucose homeostasis. In diabetes, chronic exposure to pro-inflammatory cytokines has been shown to perturb β cell communication and function. Compelling evidence has implicated extracellular vesicles (EVs...
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doaj-f6142bb336574cc9a398c46f3da9ef282021-08-26T04:33:30ZengElsevierCell Reports2211-12472021-08-01368109613Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetesNaureen Javeed0Tracy K. Her1Matthew R. Brown2Patrick Vanderboom3Kuntol Rakshit4Aoife M. Egan5Adrian Vella6Ian Lanza7Aleksey V. Matveyenko8Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA; Corresponding authorDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USADepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USADivision of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USADepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USADivision of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USADivision of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USADivision of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USADepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA; Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USASummary: Coordinated communication among pancreatic islet cells is necessary for maintenance of glucose homeostasis. In diabetes, chronic exposure to pro-inflammatory cytokines has been shown to perturb β cell communication and function. Compelling evidence has implicated extracellular vesicles (EVs) in modulating physiological and pathological responses to β cell stress. We report that pro-inflammatory β cell small EVs (cytokine-exposed EVs [cytoEVs]) induce β cell dysfunction, promote a pro-inflammatory islet transcriptome, and enhance recruitment of CD8+ T cells and macrophages. Proteomic analysis of cytoEVs shows enrichment of the chemokine CXCL10, with surface topological analysis depicting CXCL10 as membrane bound on cytoEVs to facilitate direct binding to CXCR3 receptors on the surface of β cells. CXCR3 receptor inhibition reduced CXCL10-cytoEV binding and attenuated β cell dysfunction, inflammatory gene expression, and leukocyte recruitment to islets. This work implies a significant role of pro-inflammatory β cell-derived small EVs in modulating β cell function, global gene expression, and antigen presentation through activation of the CXCL10/CXCR3 axis.http://www.sciencedirect.com/science/article/pii/S2211124721010512extracellular vesiclesβ cellinflammationdiabetesintercellular communicationCXCL10 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Naureen Javeed Tracy K. Her Matthew R. Brown Patrick Vanderboom Kuntol Rakshit Aoife M. Egan Adrian Vella Ian Lanza Aleksey V. Matveyenko |
spellingShingle |
Naureen Javeed Tracy K. Her Matthew R. Brown Patrick Vanderboom Kuntol Rakshit Aoife M. Egan Adrian Vella Ian Lanza Aleksey V. Matveyenko Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes Cell Reports extracellular vesicles β cell inflammation diabetes intercellular communication CXCL10 |
author_facet |
Naureen Javeed Tracy K. Her Matthew R. Brown Patrick Vanderboom Kuntol Rakshit Aoife M. Egan Adrian Vella Ian Lanza Aleksey V. Matveyenko |
author_sort |
Naureen Javeed |
title |
Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes |
title_short |
Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes |
title_full |
Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes |
title_fullStr |
Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes |
title_full_unstemmed |
Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes |
title_sort |
pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the cxcl10/cxcr3 axis in diabetes |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2021-08-01 |
description |
Summary: Coordinated communication among pancreatic islet cells is necessary for maintenance of glucose homeostasis. In diabetes, chronic exposure to pro-inflammatory cytokines has been shown to perturb β cell communication and function. Compelling evidence has implicated extracellular vesicles (EVs) in modulating physiological and pathological responses to β cell stress. We report that pro-inflammatory β cell small EVs (cytokine-exposed EVs [cytoEVs]) induce β cell dysfunction, promote a pro-inflammatory islet transcriptome, and enhance recruitment of CD8+ T cells and macrophages. Proteomic analysis of cytoEVs shows enrichment of the chemokine CXCL10, with surface topological analysis depicting CXCL10 as membrane bound on cytoEVs to facilitate direct binding to CXCR3 receptors on the surface of β cells. CXCR3 receptor inhibition reduced CXCL10-cytoEV binding and attenuated β cell dysfunction, inflammatory gene expression, and leukocyte recruitment to islets. This work implies a significant role of pro-inflammatory β cell-derived small EVs in modulating β cell function, global gene expression, and antigen presentation through activation of the CXCL10/CXCR3 axis. |
topic |
extracellular vesicles β cell inflammation diabetes intercellular communication CXCL10 |
url |
http://www.sciencedirect.com/science/article/pii/S2211124721010512 |
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