Per citar aquest document: http://ddd.uab.cat/record/146122
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 Maria (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)
Sànchez, Àlex (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 Luis (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 (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Data: 2015
Resum: 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.
Nota: Número d'acord de subvenció ISCIII/FIS/PI12/00195
Drets: 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
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Matèria: T cells ; Liposomes ; Apoptosis ; Insulin ; Antigen encapsulation ; Lymph nodes ; Insulitis ; Immunotherapy
Publicat a: PLoS One, Vol. 19, Issue 6 (June 2015) , p. e0127057, ISSN 1932-6203

DOI: 10.1371/journal.pone.0127057


19 p, 1.2 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Articles de recerca
Articles > Articles publicats

 Registre creat el 2016-02-08, darrera modificació el 2016-10-06



   Favorit i Compartir