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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00253/full |
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| author | Silvia Rodriguez-Fernandez Irma Pujol-Autonell Ferran Brianso Ferran Brianso David Perna-Barrull Mary Cano-Sarabia Sonia Garcia-Jimeno Adrian Villalba Alex Sanchez Alex Sanchez Eva Aguilera Federico Vazquez Joan Verdaguer Joan Verdaguer Daniel Maspoch Daniel Maspoch Marta Vives-Pi Marta Vives-Pi |
| author_facet | Silvia Rodriguez-Fernandez Irma Pujol-Autonell Ferran Brianso Ferran Brianso David Perna-Barrull Mary Cano-Sarabia Sonia Garcia-Jimeno Adrian Villalba Alex Sanchez Alex Sanchez Eva Aguilera Federico Vazquez Joan Verdaguer Joan Verdaguer Daniel Maspoch Daniel Maspoch Marta Vives-Pi Marta Vives-Pi |
| author_sort | Silvia Rodriguez-Fernandez |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T23:08:54Z |
| format | Article |
| id | doaj.art-1cbee6e539574c858b1e484df6a491fc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T23:08:54Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1cbee6e539574c858b1e484df6a491fc2022-12-21T18:47:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00253314289Phosphatidylserine-Liposomes Promote Tolerogenic Features on Dendritic Cells in Human Type 1 Diabetes by Apoptotic MimicrySilvia Rodriguez-Fernandez0Irma Pujol-Autonell1Ferran Brianso2Ferran Brianso3David Perna-Barrull4Mary Cano-Sarabia5Sonia Garcia-Jimeno6Adrian Villalba7Alex Sanchez8Alex Sanchez9Eva Aguilera10Federico Vazquez11Joan Verdaguer12Joan Verdaguer13Daniel Maspoch14Daniel Maspoch15Marta Vives-Pi16Marta Vives-Pi17Immunology Section, Germans Trias i Pujol Research Institute, Autonomous University of Barcelona, Badalona, SpainImmunology Section, Germans Trias i Pujol Research Institute, Autonomous University of Barcelona, Badalona, SpainStatistics and Bioinformatics Unit, Vall d’Hebron Research Institute, Barcelona, SpainDepartment of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, SpainImmunology Section, Germans Trias i Pujol Research Institute, Autonomous University of Barcelona, Badalona, SpainCatalan Institute of Nanoscience and Nanotechnology, CSIC and The Barcelona Institute of Science and Technology, Bellaterra, SpainCatalan Institute of Nanoscience and Nanotechnology, CSIC and The Barcelona Institute of Science and Technology, Bellaterra, SpainImmunology Section, Germans Trias i Pujol Research Institute, Autonomous University of Barcelona, Badalona, SpainStatistics and Bioinformatics Unit, Vall d’Hebron Research Institute, Barcelona, SpainDepartment of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, SpainEndocrinology Section, Germans Trias i Pujol University Hospital, Badalona, SpainEndocrinology Section, Germans Trias i Pujol University Hospital, Badalona, SpainDepartment of Experimental Medicine, University of Lleida & IRBLleida, Lleida, SpainCIBERDEM, ISCiii, Madrid, SpainCatalan Institute of Nanoscience and Nanotechnology, CSIC and The Barcelona Institute of Science and Technology, Bellaterra, SpainICREA, Barcelona, SpainImmunology Section, Germans Trias i Pujol Research Institute, Autonomous University of Barcelona, Badalona, SpainCIBERDEM, ISCiii, Madrid, SpainType 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.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00253/fullimmunotherapyautoimmunityhuman type 1 diabetesliposomestolerancedendritic cells |
| spellingShingle | Silvia Rodriguez-Fernandez Irma Pujol-Autonell Ferran Brianso Ferran Brianso David Perna-Barrull Mary Cano-Sarabia Sonia Garcia-Jimeno Adrian Villalba Alex Sanchez Alex Sanchez Eva Aguilera Federico Vazquez Joan Verdaguer Joan Verdaguer Daniel Maspoch Daniel Maspoch Marta Vives-Pi Marta Vives-Pi Phosphatidylserine-Liposomes Promote Tolerogenic Features on Dendritic Cells in Human Type 1 Diabetes by Apoptotic Mimicry Frontiers in Immunology immunotherapy autoimmunity human type 1 diabetes liposomes tolerance dendritic cells |
| title | 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_short | 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 |
| topic | immunotherapy autoimmunity human type 1 diabetes liposomes tolerance dendritic cells |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00253/full |
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