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Oral Administration of Silkworm-Produced GAD65 and Insulin Bi-Autoantigens against Type 1 Diabetes

Induction of mucosal tolerance by oral administration of protein antigens is a potential therapeutic strategy for preventing and treating type 1 diabetes (T1D); however, the requirement for a large dosage of protein limits clinical applications because of the low efficacy. In this study, we generate...

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Detalles Bibliográficos
Autores principales: Liu, Baoping, Yue, Yuan, Yang, Yun, Jin, Yongfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718521/
https://www.ncbi.nlm.nih.gov/pubmed/26783749
http://dx.doi.org/10.1371/journal.pone.0147260
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author Liu, Baoping
Yue, Yuan
Yang, Yun
Jin, Yongfeng
author_facet Liu, Baoping
Yue, Yuan
Yang, Yun
Jin, Yongfeng
author_sort Liu, Baoping
collection PubMed
description Induction of mucosal tolerance by oral administration of protein antigens is a potential therapeutic strategy for preventing and treating type 1 diabetes (T1D); however, the requirement for a large dosage of protein limits clinical applications because of the low efficacy. In this study, we generated a fusion protein CTB-Ins-GAD composed of CTB (cholera toxin B subunit), insulin, and three copies of GAD65 peptide 531–545, which were efficiently produced in silkworm pupae, to evaluate its protective effect against T1D. We demonstrate that oral administration of CTB-Ins-GAD suppressed T1D by up to 78%, which is much more effective than GAD65 single-antigen treatment. Strikingly, CTB-Ins-GAD enhance insulin- and GAD65-specific Th2-like immune responses, which repairs the Th1/Th2 imbalance and increases the number of CD4(+)CD25(+)Foxp3(+) T cell and suppresses insulin- and GAD65-reactive spleen T lymphocyte proliferation and migration. Our results strongly suggest that the combined dual antigens promote the induction of oral tolerance, thus providing an effective and economic immunotherapy against T1D in combination with a silkworm bioreactor.
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spelling pubmed-47185212016-01-30 Oral Administration of Silkworm-Produced GAD65 and Insulin Bi-Autoantigens against Type 1 Diabetes Liu, Baoping Yue, Yuan Yang, Yun Jin, Yongfeng PLoS One Research Article Induction of mucosal tolerance by oral administration of protein antigens is a potential therapeutic strategy for preventing and treating type 1 diabetes (T1D); however, the requirement for a large dosage of protein limits clinical applications because of the low efficacy. In this study, we generated a fusion protein CTB-Ins-GAD composed of CTB (cholera toxin B subunit), insulin, and three copies of GAD65 peptide 531–545, which were efficiently produced in silkworm pupae, to evaluate its protective effect against T1D. We demonstrate that oral administration of CTB-Ins-GAD suppressed T1D by up to 78%, which is much more effective than GAD65 single-antigen treatment. Strikingly, CTB-Ins-GAD enhance insulin- and GAD65-specific Th2-like immune responses, which repairs the Th1/Th2 imbalance and increases the number of CD4(+)CD25(+)Foxp3(+) T cell and suppresses insulin- and GAD65-reactive spleen T lymphocyte proliferation and migration. Our results strongly suggest that the combined dual antigens promote the induction of oral tolerance, thus providing an effective and economic immunotherapy against T1D in combination with a silkworm bioreactor. Public Library of Science 2016-01-19 /pmc/articles/PMC4718521/ /pubmed/26783749 http://dx.doi.org/10.1371/journal.pone.0147260 Text en © 2016 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Liu, Baoping
Yue, Yuan
Yang, Yun
Jin, Yongfeng
Oral Administration of Silkworm-Produced GAD65 and Insulin Bi-Autoantigens against Type 1 Diabetes
title Oral Administration of Silkworm-Produced GAD65 and Insulin Bi-Autoantigens against Type 1 Diabetes
title_full Oral Administration of Silkworm-Produced GAD65 and Insulin Bi-Autoantigens against Type 1 Diabetes
title_fullStr Oral Administration of Silkworm-Produced GAD65 and Insulin Bi-Autoantigens against Type 1 Diabetes
title_full_unstemmed Oral Administration of Silkworm-Produced GAD65 and Insulin Bi-Autoantigens against Type 1 Diabetes
title_short Oral Administration of Silkworm-Produced GAD65 and Insulin Bi-Autoantigens against Type 1 Diabetes
title_sort oral administration of silkworm-produced gad65 and insulin bi-autoantigens against type 1 diabetes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718521/
https://www.ncbi.nlm.nih.gov/pubmed/26783749
http://dx.doi.org/10.1371/journal.pone.0147260
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