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Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes
Pujol-Autonell, Irma (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Serracant Prat, Arnau (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cano-Sarabia, Mary (Institut Català de Nanociència i Nanotecnologia)
Ampudia Carrasco, Rosa María (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rodriguez Fernandez, Silvia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sánchez, Alex (Sànchez Pla) (Universitat de Barcelona. Departament d'Estadística)
Izquierdo Castro, Cristina (Universitat de Barcelona. Departament de Fisiologia i Immunologia)
Stratmann, Thomas (Universitat de Barcelona. Departament de Fisiologia i Immunologia)
Puig Domingo, Manuel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Maspoch Comamala, Daniel (Institut Català de Nanociència i Nanotecnologia)
Verdaguer, Joan (Universitat de Lleida. Departament de Medicina Experimental)
Vives Pi, Marta (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Universitat Autònoma de Barcelona

Fecha: 2015
Resumen: 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.
Ayudas: Instituto de Salud Carlos III FIS/PI12/00195
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Lengua: Anglès
Documento: Article ; recerca ; Versió publicada
Materia: T cells ; Liposomes ; Apoptosis ; Insulin ; Antigen encapsulation ; Lymph nodes ; Insulitis ; Immunotherapy
Publicado en: PloS one, Vol. 19, Issue 6 (June 2015) , p. e0127057, ISSN 1932-6203

DOI: 10.1371/journal.pone.0127057
PMID: 26039878


19 p, 1.2 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias > Institut Català de Nanociència i Nanotecnologia (ICN2)
Artículos > Artículos de investigación
Artículos > Artículos publicados

 Registro creado el 2016-02-08, última modificación el 2023-04-11



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