Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes.

Autor:	Javeed N; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: javeed.naureen@mayo.edu., Her TK; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA., Brown MR; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA., Vanderboom P; Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USA., Rakshit K; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA., Egan AM; Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USA., Vella A; Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USA., Lanza I; Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USA., Matveyenko AV; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA; Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, MN 55905, USA.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Aug 24; Vol. 36 (8), pp. 109613.
DOI:	10.1016/j.celrep.2021.109613
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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