Aiello, SistianaRocchetta, FedericaLongaretti, LorenaFaravelli, SilviaTodeschini, MartaCassis, Linda, 1977-Pezzuto, FrancescaTomasoni, SusannaAzzollini, NadiMister, MarilenaMele, CaterinaConti, SaraBreno, MatteRemuzzi, GiuseppeNoris, MarinaBenigni, Ariela2018-07-262018-07-262017Aiello S, Rocchetta F, Longaretti L, Faravelli S, Todeschini M, Cassis L. et al. Extracellular vesicles derived from T regulatory cells suppress T cell proliferation and prolong allograft survival. Sci Rep. 2017 Sep 14;7(1):11518. DOI: 10.1038/s41598-017-08617-32045-2322http://hdl.handle.net/10230/35269We have previously shown that rat allogeneic DC, made immature by adenoviral gene transfer of the dominant negative form of IKK2, gave rise in-vitro to a unique population of CD4+CD25- regulatory T cells (dnIKK2-Treg). These cells inhibited Tcell response in-vitro, without needing cell-to-cell contact, and induced kidney allograft survival prolongation in-vivo. Deep insight into the mechanisms behind dnIKK2-Treg-induced suppression of Tcell proliferation remained elusive. Here we document that dnIKK2-Treg release extracellular vesicles (EV) riched in exosomes, fully accounting for the cell-contact independent immunosuppressive activity of parent cells. DnIKK2-Treg-EV contain a unique molecular cargo of specific miRNAs and iNOS, which, once delivered into target cells, blocked cell cycle progression and induced apoptosis. DnIKK2-Treg-EV-exposed T cells were in turn converted into regulatory cells. Notably, when administered in-vivo, dnIKK2-Treg-EV prolonged kidney allograft survival. DnIKK2-Treg-derived EV could be a tool for manipulating the immune system and for discovering novel potential immunosuppressive molecules in the context of allotransplantation.application/pdfengCopyright © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Ronyons -- MalaltiesGenèticainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-017-08617-3info:eu-repo/semantics/openAccess