Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone
Sang-Hyun Kim, Jun-Hyeok Moon, Seong-Un Jeong, Ho-Hyun Jung, Chan-Su Park, Bang Yeon Hwang, Chong-Kil LeeCollege of Pharmacy, Chungbuk National University, Cheongju, KoreaPurpose: Dexamethasone (Dex) has long been used as a potent immunosuppressive agent in the treatment of inflammatory and autoimmu...
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Dove Medical Press
2019
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oai:doaj.org-article:eac98eab5b3141de91a23faab0982f462021-12-02T03:06:29ZInduction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone1178-2013https://doaj.org/article/eac98eab5b3141de91a23faab0982f462019-07-01T00:00:00Zhttps://www.dovepress.com/induction-of-antigen-specific-immune-tolerance-using-biodegradable-nan-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sang-Hyun Kim, Jun-Hyeok Moon, Seong-Un Jeong, Ho-Hyun Jung, Chan-Su Park, Bang Yeon Hwang, Chong-Kil LeeCollege of Pharmacy, Chungbuk National University, Cheongju, KoreaPurpose: Dexamethasone (Dex) has long been used as a potent immunosuppressive agent in the treatment of inflammatory and autoimmune diseases, despite serious side effects. In the present study, Dex and model antigen ovalbumin (OVA) were encapsulated with poly(lactic-co-glycolic acid) to deliver Dex and OVA preferentially to phagocytic cells, reducing systemic side effects of Dex. The OVA-specific immune tolerance-inducing activity of the nanoparticles (NPs) was examined.Methods: Polymeric NPs containing OVA and Dex (NP[OVA+Dex]) were prepared by the water-in-oil-in-water double emulsion solvent evaporation method. The effects of NP[OVA+Dex] on the maturation and function of immature dendritic cells (DCs) were examined in vitro. Furthermore, the OVA-specific immune tolerizing effects of NP[OVA+Dex] were confirmed in mice that were intravenously injected or orally fed with the NPs.Results: Immature DCs treated in vitro with NP[OVA+Dex] did not mature into immunogenic DCs but instead were converted into tolerogenic DCs. Furthermore, profoundly suppressed generation of OVA-specific cytotoxic T cells and production of OVA-specific IgG were observed in mice injected with NP[OVA+Dex], whereas regulatory T cells were concomitantly increased. Feeding of mice with NP[OVA+Dex] also induced OVA-specific immune tolerance.Conclusion: The present study demonstrates that oral feeding as well as intravenous injection of poly(lactic-co-glycolic acid) NPs encapsulating both antigen and Dex is a useful means of inducing antigen-specific immune tolerance, which is crucial for the treatment of autoimmune diseases.Keywords: polymeric nanoparticle, dexamethasone, ovalbumin, tolerogenic dendritic cell, antigen-specific immune toleranceKim SHMoon JHJeong SUJung HHPark CSHwang BYLee CKDove Medical PressarticlePolymeric nanoparticleDexamethasoneOvalbuminTolerogenic dendritic cellAntigen-specific immune toleranceMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5229-5242 (2019) |
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Polymeric nanoparticle Dexamethasone Ovalbumin Tolerogenic dendritic cell Antigen-specific immune tolerance Medicine (General) R5-920 |
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Polymeric nanoparticle Dexamethasone Ovalbumin Tolerogenic dendritic cell Antigen-specific immune tolerance Medicine (General) R5-920 Kim SH Moon JH Jeong SU Jung HH Park CS Hwang BY Lee CK Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone |
description |
Sang-Hyun Kim, Jun-Hyeok Moon, Seong-Un Jeong, Ho-Hyun Jung, Chan-Su Park, Bang Yeon Hwang, Chong-Kil LeeCollege of Pharmacy, Chungbuk National University, Cheongju, KoreaPurpose: Dexamethasone (Dex) has long been used as a potent immunosuppressive agent in the treatment of inflammatory and autoimmune diseases, despite serious side effects. In the present study, Dex and model antigen ovalbumin (OVA) were encapsulated with poly(lactic-co-glycolic acid) to deliver Dex and OVA preferentially to phagocytic cells, reducing systemic side effects of Dex. The OVA-specific immune tolerance-inducing activity of the nanoparticles (NPs) was examined.Methods: Polymeric NPs containing OVA and Dex (NP[OVA+Dex]) were prepared by the water-in-oil-in-water double emulsion solvent evaporation method. The effects of NP[OVA+Dex] on the maturation and function of immature dendritic cells (DCs) were examined in vitro. Furthermore, the OVA-specific immune tolerizing effects of NP[OVA+Dex] were confirmed in mice that were intravenously injected or orally fed with the NPs.Results: Immature DCs treated in vitro with NP[OVA+Dex] did not mature into immunogenic DCs but instead were converted into tolerogenic DCs. Furthermore, profoundly suppressed generation of OVA-specific cytotoxic T cells and production of OVA-specific IgG were observed in mice injected with NP[OVA+Dex], whereas regulatory T cells were concomitantly increased. Feeding of mice with NP[OVA+Dex] also induced OVA-specific immune tolerance.Conclusion: The present study demonstrates that oral feeding as well as intravenous injection of poly(lactic-co-glycolic acid) NPs encapsulating both antigen and Dex is a useful means of inducing antigen-specific immune tolerance, which is crucial for the treatment of autoimmune diseases.Keywords: polymeric nanoparticle, dexamethasone, ovalbumin, tolerogenic dendritic cell, antigen-specific immune tolerance |
format |
article |
author |
Kim SH Moon JH Jeong SU Jung HH Park CS Hwang BY Lee CK |
author_facet |
Kim SH Moon JH Jeong SU Jung HH Park CS Hwang BY Lee CK |
author_sort |
Kim SH |
title |
Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone |
title_short |
Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone |
title_full |
Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone |
title_fullStr |
Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone |
title_full_unstemmed |
Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone |
title_sort |
induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone |
publisher |
Dove Medical Press |
publishDate |
2019 |
url |
https://doaj.org/article/eac98eab5b3141de91a23faab0982f46 |
work_keys_str_mv |
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