Phosphatidylserine-liposomes Promote Tolerogenic Features on Dendritic cells in human Type 1 Diabetes by apoptotic Mimicry

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2018Author
Rodríguez Fernández, Silvia
Pujol Autonell, Irma
Briansó Castilla, Ferran
Perna Barrull, David
Cano Sarabia, Antonia María
García Jimeno, Sonia
Villalba, Adrian
Sánchez (Sànchez Pla), Álex
Aguilera, Eva
Vázquez San Miguel, Federico
Maspoch, Daniel
Vives Pi, Marta
Suggested citation
Rodríguez Fernández, Silvia;
Pujol Autonell, Irma;
Briansó Castilla, Ferran;
Perna Barrull, David;
Cano Sarabia, Antonia María;
García Jimeno, Sonia;
...
Vives Pi, Marta.
(2018)
.
Phosphatidylserine-liposomes Promote Tolerogenic Features on Dendritic cells in human Type 1 Diabetes by apoptotic Mimicry.
Frontiers in Immunology, 2018, vol. 9, a253.
https://doi.org/10.3389/fimmu.2018.00253.
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Show full item recordAbstract
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.
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Frontiers in Immunology, 2018, vol. 9, a253European research projects
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