Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes

This is an open access article distributed under the terms of the Creative Commons Attribution License.-- et al.

Detalles Bibliográficos
Autores: Pujol-Autonell, Irma, Cano-Sarabia, Mary, Maspoch, Daniel, Vives-Pi, Marta
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/143164
Acceso en línea:http://hdl.handle.net/10261/143164
Access Level:acceso abierto
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spelling Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetesPujol-Autonell, IrmaCano-Sarabia, MaryMaspoch, DanielVives-Pi, MartaThis is an open access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Introduction]: The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes.[Objective]: To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes.[Methods]: A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides.[Results]: We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion.[Conclusions]: We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for autoimmune diseases.This work was supported by a grant from Spanish Government (FIS PI12/00195). IPA was supported by AGAUR, Generalitat de Catalunya. MVP and RA are supported by the Health Dept. of the Catalan Government, Generalitat de Catalunya.Peer reviewedPublic Library of ScienceGeneralitat de CatalunyaInstituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201720172015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/143164reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1371/journal.pone.0127057Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1431642026-05-22T06:33:51Z
dc.title.none.fl_str_mv Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes
title Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes
spellingShingle Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes
Pujol-Autonell, Irma
title_short Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes
title_full Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes
title_fullStr Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes
title_full_unstemmed Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes
title_sort Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes
dc.creator.none.fl_str_mv Pujol-Autonell, Irma
Cano-Sarabia, Mary
Maspoch, Daniel
Vives-Pi, Marta
author Pujol-Autonell, Irma
author_facet Pujol-Autonell, Irma
Cano-Sarabia, Mary
Maspoch, Daniel
Vives-Pi, Marta
author_role author
author2 Cano-Sarabia, Mary
Maspoch, Daniel
Vives-Pi, Marta
author2_role author
author
author
dc.contributor.none.fl_str_mv Generalitat de Catalunya
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description This is an open access article distributed under the terms of the Creative Commons Attribution License.-- et al.
publishDate 2015
dc.date.none.fl_str_mv 2015
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/143164
url http://hdl.handle.net/10261/143164
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1371/journal.pone.0127057

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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