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Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with the Treg/Th17 cell balance

BACKGROUND: Foxp3 is a key regulator of the development and function of regulatory T cells (Tregs), and its expression is thought to be T cell-restricted. We found that B cells in mice can express Foxp3 and B cells expressing Foxp3 may play a role in preventing the development of collagen-induced ar...

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Autores principales: Park, Mi Kyung, Jung, Young Ok, Lee, Seon-Yeong, Lee, Seung Hoon, Heo, Yu Jung, Kim, Eun Kyung, Oh, Hye Jwa, Moon, Young Mee, Son, Hye-Jin, Park, Min Jung, Park, Sung Hwan, Kim, Ho Youn, La Cho, Mi, Min, Jun Ki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924280/
https://www.ncbi.nlm.nih.gov/pubmed/27350539
http://dx.doi.org/10.1186/s12967-016-0940-7
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author Park, Mi Kyung
Jung, Young Ok
Lee, Seon-Yeong
Lee, Seung Hoon
Heo, Yu Jung
Kim, Eun Kyung
Oh, Hye Jwa
Moon, Young Mee
Son, Hye-Jin
Park, Min Jung
Park, Sung Hwan
Kim, Ho Youn
La Cho, Mi
Min, Jun Ki
author_facet Park, Mi Kyung
Jung, Young Ok
Lee, Seon-Yeong
Lee, Seung Hoon
Heo, Yu Jung
Kim, Eun Kyung
Oh, Hye Jwa
Moon, Young Mee
Son, Hye-Jin
Park, Min Jung
Park, Sung Hwan
Kim, Ho Youn
La Cho, Mi
Min, Jun Ki
author_sort Park, Mi Kyung
collection PubMed
description BACKGROUND: Foxp3 is a key regulator of the development and function of regulatory T cells (Tregs), and its expression is thought to be T cell-restricted. We found that B cells in mice can express Foxp3 and B cells expressing Foxp3 may play a role in preventing the development of collagen-induced arthritis (CIA) in DBA/1J mice. METHODS: Foxp3 expression was modulated in CD19(+) B cells by transfection with shRNA or using an over-expression construct. In addition, Foxp3-transfected B cells were adoptively transferred to CIA mice. We found that LPS or anti-IgM stimulation induced Foxp3 expression in B cells. Foxp3-expressing B cells were found in the spleens of mice. RESULTS: Over-expression of Foxp3 conferred a contact-dependent suppressive ability on proliferation of responder T cells. Down-regulation of Foxp3 by shRNA caused a profound induction in proliferation of responder T cells. Adoptive transfer of Foxp3(+)CD19(+) B cells attenuated the clinical symptoms of CIA significantly with concomitant suppression of IL-17 production and enhancement of Foxp3 expression in CD4(+) T cells from splenocytes. CONCLUSION: Our data indicate that Foxp3 expression is not restricted to T cells. The expression of Foxp3 in B cells is critical for the immunoregulation of T cells and limits autoimmunity in a mouse model.
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spelling pubmed-49242802016-06-29 Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with the Treg/Th17 cell balance Park, Mi Kyung Jung, Young Ok Lee, Seon-Yeong Lee, Seung Hoon Heo, Yu Jung Kim, Eun Kyung Oh, Hye Jwa Moon, Young Mee Son, Hye-Jin Park, Min Jung Park, Sung Hwan Kim, Ho Youn La Cho, Mi Min, Jun Ki J Transl Med Research BACKGROUND: Foxp3 is a key regulator of the development and function of regulatory T cells (Tregs), and its expression is thought to be T cell-restricted. We found that B cells in mice can express Foxp3 and B cells expressing Foxp3 may play a role in preventing the development of collagen-induced arthritis (CIA) in DBA/1J mice. METHODS: Foxp3 expression was modulated in CD19(+) B cells by transfection with shRNA or using an over-expression construct. In addition, Foxp3-transfected B cells were adoptively transferred to CIA mice. We found that LPS or anti-IgM stimulation induced Foxp3 expression in B cells. Foxp3-expressing B cells were found in the spleens of mice. RESULTS: Over-expression of Foxp3 conferred a contact-dependent suppressive ability on proliferation of responder T cells. Down-regulation of Foxp3 by shRNA caused a profound induction in proliferation of responder T cells. Adoptive transfer of Foxp3(+)CD19(+) B cells attenuated the clinical symptoms of CIA significantly with concomitant suppression of IL-17 production and enhancement of Foxp3 expression in CD4(+) T cells from splenocytes. CONCLUSION: Our data indicate that Foxp3 expression is not restricted to T cells. The expression of Foxp3 in B cells is critical for the immunoregulation of T cells and limits autoimmunity in a mouse model. BioMed Central 2016-06-28 /pmc/articles/PMC4924280/ /pubmed/27350539 http://dx.doi.org/10.1186/s12967-016-0940-7 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Park, Mi Kyung
Jung, Young Ok
Lee, Seon-Yeong
Lee, Seung Hoon
Heo, Yu Jung
Kim, Eun Kyung
Oh, Hye Jwa
Moon, Young Mee
Son, Hye-Jin
Park, Min Jung
Park, Sung Hwan
Kim, Ho Youn
La Cho, Mi
Min, Jun Ki
Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with the Treg/Th17 cell balance
title Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with the Treg/Th17 cell balance
title_full Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with the Treg/Th17 cell balance
title_fullStr Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with the Treg/Th17 cell balance
title_full_unstemmed Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with the Treg/Th17 cell balance
title_short Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with the Treg/Th17 cell balance
title_sort amelioration of autoimmune arthritis by adoptive transfer of foxp3-expressing regulatory b cells is associated with the treg/th17 cell balance
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924280/
https://www.ncbi.nlm.nih.gov/pubmed/27350539
http://dx.doi.org/10.1186/s12967-016-0940-7
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