Extracellular vesicles derived from stressed beta cells mediate monocyte activation and contribute to islet inflammation
Frontiers in Immunology, vol. 15, pp. 1393248
Abstract
Objective: Beta cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In recent years, the role played by beta cells in the development of T1D has evolved from passive victims of the immune system to active contributors in their own destruction. We and others have demonstrated that perturbations in the islet microenvironment promote endoplasmic reticulum (ER) stress in beta cells, leading to enhanced immunogenicity. Among the underlying mechanisms, secretion of extracellular vesicles (EVs) by beta cells has been suggested to mediate the crosstalk with the immune cell compartment. Methods: , which encodes BiP/GRP78, in EndoC-βH1 cells. To investigate the role of EVs in the interaction between beta cells and the immune system, we characterized the EV miRNA cargo and evaluated their effect on innate immune cells. Results: knockdown resulted in the upregulation of signaling pathways involved in the unfolded protein response (UPR) and changes the miRNA content of EVs, including reduced levels of miRNAs involved in IL-1β signaling. Treatment of primary human monocytes with EVs from stressed beta cells resulted in increased surface expression of CD11b, HLA-DR, CD40 and CD86 and upregulation of IL-1β and IL-6. Conclusion: These findings indicate that the content of EVs derived from stressed beta cells can be a mediator of islet inflammation.
Authors 9
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Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
Leiden University Center of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center · Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Amsterdam Vesicle Center, Biomedical Engineering and Physics and Laboratory of Experimental Clinical Chemistry, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
Oncode institute, Leiden University Medical Center, Leiden, Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Bruno Guigas Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
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