Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicry

Type 1 diabetes (T1D) is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow β-cell recovery has become vital. Relying on the inherent ability of apoptotic...

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Autores: Rodríguez Fernández, Silvia, Pujol Autonell, Irma, Briansó, Ferran, Perna Barrull, David, Cano Sarabia, Mary, García Jimeno, Sonia, Villalba, Adrián, Sànchez, Àlex (Sànchez Pla), Aguilera, Eva, Vázquez, Federico, Verdaguer, Joan, Maspoch, Daniel, Vives Pi, Marta
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/176613
Acceso en línea:https://hdl.handle.net/2445/176613
Access Level:acceso abierto
Palabra clave:Diabetis
Liposomes
Cèl·lules dendrítiques
Diabetes
Dendritic cells
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spelling Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicryRodríguez Fernández, SilviaPujol Autonell, IrmaBriansó, FerranPerna Barrull, DavidCano Sarabia, MaryGarcía Jimeno, SoniaVillalba, AdriánSànchez, Àlex (Sànchez Pla)Aguilera, EvaVázquez, FedericoVerdaguer, JoanMaspoch, DanielVives Pi, MartaDiabetisLiposomesCèl·lules dendrítiquesDiabetesLiposomesDendritic cellsType 1 diabetes (T1D) is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow β-cell recovery has become vital. Relying on the inherent ability of apoptotic cells to induce immunological tolerance, we demonstrated that liposomes mimicking apoptotic β-cells arrested autoimmunity to β-cells and prevented experimental T1D through tolerogenic dendritic cell (DC) generation. These liposomes contained phosphatidylserine (PS)-the main signal of the apoptotic cell membrane-and β-cell autoantigens. To move toward a clinical application, PS-liposomes with optimum size and composition for phagocytosis were loaded with human insulin peptides and tested on DCs from patients with T1D and control age-related subjects. PS accelerated phagocytosis of liposomes with a dynamic typical of apoptotic cell clearance, preserving DCs viability. After PS-liposomes phagocytosis, the expression pattern of molecules involved in efferocytosis, antigen presentation, immunoregulation, and activation in DCs concurred with a tolerogenic functionality, both in patients and control subjects. Furthermore, DCs exposed to PS-liposomes displayed decreased ability to stimulate autologous T cell proliferation. Moreover, transcriptional changes in DCs from patients with T1D after PS-liposomes phagocytosis pointed to an immunoregulatory prolife. Bioinformatics analysis showed 233 differentially expressed genes. Genes involved in antigen presentation were downregulated, whereas genes pertaining to tolerogenic/anti-inflammatory pathways were mostly upregulated. In conclusion, PS-liposomes phagocytosis mimics efferocytosis and leads to phenotypic and functional changes in human DCs, which are accountable for tolerance induction. The herein reported results reinforce the potential of this novel immunotherapy to re-establish immunological tolerance, opening the door to new therapeutic approaches in the field of autoimmunity.Frontiers Media2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/176613Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2018.00253Frontiers in Immunology, 2018, vol. 9, p. 253https://doi.org/10.3389/fimmu.2018.00253cc-by (c) Rodríguez Fernández, Silvia et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1766132026-05-27T06:46:51Z
dc.title.none.fl_str_mv Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicry
title Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicry
spellingShingle Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicry
Rodríguez Fernández, Silvia
Diabetis
Liposomes
Cèl·lules dendrítiques
Diabetes
Liposomes
Dendritic cells
title_short Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicry
title_full Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicry
title_fullStr Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicry
title_full_unstemmed Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicry
title_sort Phosphatidylserine-Liposomes promote tolerogenic features on dendritic cells in human type 1 diabetes by apoptotic mimicry
dc.creator.none.fl_str_mv Rodríguez Fernández, Silvia
Pujol Autonell, Irma
Briansó, Ferran
Perna Barrull, David
Cano Sarabia, Mary
García Jimeno, Sonia
Villalba, Adrián
Sànchez, Àlex (Sànchez Pla)
Aguilera, Eva
Vázquez, Federico
Verdaguer, Joan
Maspoch, Daniel
Vives Pi, Marta
author Rodríguez Fernández, Silvia
author_facet Rodríguez Fernández, Silvia
Pujol Autonell, Irma
Briansó, Ferran
Perna Barrull, David
Cano Sarabia, Mary
García Jimeno, Sonia
Villalba, Adrián
Sànchez, Àlex (Sànchez Pla)
Aguilera, Eva
Vázquez, Federico
Verdaguer, Joan
Maspoch, Daniel
Vives Pi, Marta
author_role author
author2 Pujol Autonell, Irma
Briansó, Ferran
Perna Barrull, David
Cano Sarabia, Mary
García Jimeno, Sonia
Villalba, Adrián
Sànchez, Àlex (Sànchez Pla)
Aguilera, Eva
Vázquez, Federico
Verdaguer, Joan
Maspoch, Daniel
Vives Pi, Marta
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Diabetis
Liposomes
Cèl·lules dendrítiques
Diabetes
Liposomes
Dendritic cells
topic Diabetis
Liposomes
Cèl·lules dendrítiques
Diabetes
Liposomes
Dendritic cells
description Type 1 diabetes (T1D) is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow β-cell recovery has become vital. Relying on the inherent ability of apoptotic cells to induce immunological tolerance, we demonstrated that liposomes mimicking apoptotic β-cells arrested autoimmunity to β-cells and prevented experimental T1D through tolerogenic dendritic cell (DC) generation. These liposomes contained phosphatidylserine (PS)-the main signal of the apoptotic cell membrane-and β-cell autoantigens. To move toward a clinical application, PS-liposomes with optimum size and composition for phagocytosis were loaded with human insulin peptides and tested on DCs from patients with T1D and control age-related subjects. PS accelerated phagocytosis of liposomes with a dynamic typical of apoptotic cell clearance, preserving DCs viability. After PS-liposomes phagocytosis, the expression pattern of molecules involved in efferocytosis, antigen presentation, immunoregulation, and activation in DCs concurred with a tolerogenic functionality, both in patients and control subjects. Furthermore, DCs exposed to PS-liposomes displayed decreased ability to stimulate autologous T cell proliferation. Moreover, transcriptional changes in DCs from patients with T1D after PS-liposomes phagocytosis pointed to an immunoregulatory prolife. Bioinformatics analysis showed 233 differentially expressed genes. Genes involved in antigen presentation were downregulated, whereas genes pertaining to tolerogenic/anti-inflammatory pathways were mostly upregulated. In conclusion, PS-liposomes phagocytosis mimics efferocytosis and leads to phenotypic and functional changes in human DCs, which are accountable for tolerance induction. The herein reported results reinforce the potential of this novel immunotherapy to re-establish immunological tolerance, opening the door to new therapeutic approaches in the field of autoimmunity.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/176613
url https://hdl.handle.net/2445/176613
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2018.00253
Frontiers in Immunology, 2018, vol. 9, p. 253
https://doi.org/10.3389/fimmu.2018.00253
dc.rights.none.fl_str_mv cc-by (c) Rodríguez Fernández, Silvia et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Rodríguez Fernández, Silvia et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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