@article{38ff62ce83a84730ae2cdfcf953d9e2b,
title = "Extracellular Vesicles Derived Human-miRNAs Modulate the Immune System in Type 1 Diabetes",
abstract = "Extracellular vesicles with their molecular cargo can modulate target cell response and may affect the pathogenesis of diseases. The extracellular vesicles containing micro-RNAs (miRNAs), which are often studied as disease biomarkers, but rarely as mediators of the disease development. The role of extracellular vesicles derived miRNAs in type 1 diabetes is currently not well established. We observed a fraction of blood plasma extracellular vesicles positive for membrane proteins potentially associated with insulin-producing beta-cells and identified differentially expressed extracellular vesicles derived miRNAs in individuals with type 1 diabetes. These differentially expressed extracellular vesicles derived human miRNAs in participants with type 1 diabetes and participants with Langerhans islets beta-cells destruction showed the ability to activate TLR7/8 signaling cascade and increase activation as well as cytotoxicity of the effector blood immune cells with cytokine and chemokine release. Our results illustrate extracellular vesicles derived human miRNAs as modulators of the immune system in type 1 diabetes autoimmunity, providing potentially new insight into the pathogenesis of the disease, and novel molecular targets for intervention and type 1 diabetes prevention.",
keywords = "autoimmune disease, extracellular vesicles, immune modulating activity, miRNA, TLR7/8, type 1 diabetes",
author = "Tine Tesovnik and Jernej Kova{\v c} and Katka Pohar and Samo Hudoklin and Klemen Dov{\v c} and Nata{\v s}a Bratina and {Trebu{\v s}ak Podkraj{\v s}ek}, Katarina and Maru{\v s}a Debeljak and Peter Verani{\v c} and Emanuele Bosi and Lorenzo Piemonti and Alojz Ihan and Tadej Battelino",
note = "Funding Information: We thank prof. Michael Hackenberg and sRNA developer team for their technical support with sRNAtoolBox data analysis. We also thank T1D participants and their families, healthy control participants, Brigita Mali, and nursing team of the University Children?s Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases. Funding. This work was supported by the Slovenian Research Agency under grant P3-0343, P3-0108, and the University Medical Centre Ljubljana grant 20160161. Human islets were provided by the San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele (Milan), within the European islet distribution program for basic research supported by JDRF (2-RSC-2019-724-I-X). This project received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 115797 (INNODIA). This Joint Undertaking receives support from the Union?s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations, JDRF, and The Leona M. and Harry B. Helmsley Charitable Trust. Funding Information: This work was supported by the Slovenian Research Agency under grant P3-0343, P3-0108, and the University Medical Centre Ljubljana grant 20160161. Human islets were provided by the San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele (Milan), within the European islet distribution program for basic research supported by JDRF (2-RSC-2019-724-I-X). This project received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 115797 (INNODIA). This Joint Undertaking receives support from the Union{\textquoteright}s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations, JDRF, and The Leona M. and Harry B. Helmsley Charitable Trust. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Tesovnik, Kova{\v c}, Pohar, Hudoklin, Dov{\v c}, Bratina, Trebu{\v s}ak Podkraj{\v s}ek, Debeljak, Verani{\v c}, Bosi, Piemonti, Ihan and Battelino. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = mar,
day = "31",
doi = "10.3389/fcell.2020.00202",
language = "English",
volume = "8",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media S. A.",
}