Use of Autoantigen-Loaded Phosphatidylserine-Liposomes to Arrest Autoimmunity in Type 1 Diabetes

Pujol Autonell, Irma; Serracant Prat, Arnau; Cano Sarabia, Antonia María; Ampudia, Rosa Maria; Rodríguez Fernández, Silvia; Sánchez (Sànchez Pla), Álex; Izquierdo, Cristina; Stratmann, Thomas; Puig-Domingo, Manuel; Maspoch, Daniel; Verdaguer Autonell, Joan; Vives Pi, Marta

doi:https://doi.org/10.1371/journal.pone.0127057

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2015-06-03

Author

Pujol Autonell, Irma

Serracant Prat, Arnau

Cano Sarabia, Antonia María

Ampudia, Rosa Maria

Rodríguez Fernández, Silvia

Sánchez (Sànchez Pla), Álex

Izquierdo, Cristina

Stratmann, Thomas

Puig-Domingo, Manuel

Maspoch, Daniel

Verdaguer Autonell, Joan

Vives Pi, Marta

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Pujol Autonell, Irma; Serracant Prat, Arnau; Cano Sarabia, Antonia María; Ampudia, Rosa Maria; Rodríguez Fernández, Silvia; Sánchez (Sànchez Pla), Álex; ... Vives Pi, Marta. (2015) . Use of Autoantigen-Loaded Phosphatidylserine-Liposomes to Arrest Autoimmunity in Type 1 Diabetes. PLoS One, 2015, vol. 10, núm.6, e0127057. https://doi.org/10.1371/journal.pone.0127057.

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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 a-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 a-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.

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http://hdl.handle.net/10459.1/48676

DOI

https://doi.org/10.1371/journal.pone.0127057

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PLoS One, 2015, vol. 10, núm.6, e0127057

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Except where otherwise noted, this item's license is described as cc-by, (c) Pujol Autonell, Irma et al., 2015