In vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production

Abstract Available therapeutics for autoimmune disorders focused on mitigating symptoms, rather than treating the cause of the disorder. A novel approach using adeno-associated virus (AAV) could restore tolerance to the autoimmune targets and provide a permanent treatment for autoimmune diseases. He...

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Autores principales:	Matthew Wade, Hugues Fausther-Bovendo, Marc-Antoine De La Vega, Gary Kobinger
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/46587e0ae2a64831ab66f65f12b4a139
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spelling	oai:doaj.org-article:46587e0ae2a64831ab66f65f12b4a1392021-12-02T18:34:01ZIn vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production10.1038/s41598-021-97739-w2045-2322https://doaj.org/article/46587e0ae2a64831ab66f65f12b4a1392021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97739-whttps://doaj.org/toc/2045-2322Abstract Available therapeutics for autoimmune disorders focused on mitigating symptoms, rather than treating the cause of the disorder. A novel approach using adeno-associated virus (AAV) could restore tolerance to the autoimmune targets and provide a permanent treatment for autoimmune diseases. Here, we evaluated the ability of collagen II T-cell epitopes packaged in adeno-associated virus serotype 8 (AAV-8) vectors to reduce pathogenic cellular and humoral responses against collagen and to mitigate the disease in the collagen-induced arthritis mouse model. The cytokines and immune cells involved in the immune suppression were also investigated. Mice treated with AAV-8 containing collagen II T-cell epitopes demonstrated a significant reduction in the arthritis symptoms, pathogenic collagen specific antibody and T cell responses. The AAV-8 mediated immune suppression was mediated by increased interleukin-10 expression and regulatory T cells expansion. Altogether, this study strengthens the notion that AAV vectors are promising candidates for the treatment of autoimmune diseases.Matthew WadeHugues Fausther-BovendoMarc-Antoine De La VegaGary KobingerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew Wade Hugues Fausther-Bovendo Marc-Antoine De La Vega Gary Kobinger In vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production
description	Abstract Available therapeutics for autoimmune disorders focused on mitigating symptoms, rather than treating the cause of the disorder. A novel approach using adeno-associated virus (AAV) could restore tolerance to the autoimmune targets and provide a permanent treatment for autoimmune diseases. Here, we evaluated the ability of collagen II T-cell epitopes packaged in adeno-associated virus serotype 8 (AAV-8) vectors to reduce pathogenic cellular and humoral responses against collagen and to mitigate the disease in the collagen-induced arthritis mouse model. The cytokines and immune cells involved in the immune suppression were also investigated. Mice treated with AAV-8 containing collagen II T-cell epitopes demonstrated a significant reduction in the arthritis symptoms, pathogenic collagen specific antibody and T cell responses. The AAV-8 mediated immune suppression was mediated by increased interleukin-10 expression and regulatory T cells expansion. Altogether, this study strengthens the notion that AAV vectors are promising candidates for the treatment of autoimmune diseases.
format	article
author	Matthew Wade Hugues Fausther-Bovendo Marc-Antoine De La Vega Gary Kobinger
author_facet	Matthew Wade Hugues Fausther-Bovendo Marc-Antoine De La Vega Gary Kobinger
author_sort	Matthew Wade
title	In vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production
title_short	In vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production
title_full	In vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production
title_fullStr	In vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production
title_full_unstemmed	In vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production
title_sort	in vivo generation of collagen specific tregs with aav8 suppresses autoimmune responses and arthritis in dba1 mice through il10 production
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/46587e0ae2a64831ab66f65f12b4a139
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_version_	1718377915729575936

In vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production

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