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Selective Impairment of T(H)17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes

The inhibition of apoptotic cell death in T cells through the dysregulated expression of BCL2 family members has been associated with the protection against the development of different autoimmune diseases. However, multiple mechanisms were proposed to be responsible for such protective effect. The...

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Autores principales: Iglesias, Marcos, Augustin, Juan Jesús, Alvarez, Pilar, Santiuste, Inés, Postigo, Jorge, Merino, Jesús, Merino, Ramón
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951111/
https://www.ncbi.nlm.nih.gov/pubmed/27433938
http://dx.doi.org/10.1371/journal.pone.0159714
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author Iglesias, Marcos
Augustin, Juan Jesús
Alvarez, Pilar
Santiuste, Inés
Postigo, Jorge
Merino, Jesús
Merino, Ramón
author_facet Iglesias, Marcos
Augustin, Juan Jesús
Alvarez, Pilar
Santiuste, Inés
Postigo, Jorge
Merino, Jesús
Merino, Ramón
author_sort Iglesias, Marcos
collection PubMed
description The inhibition of apoptotic cell death in T cells through the dysregulated expression of BCL2 family members has been associated with the protection against the development of different autoimmune diseases. However, multiple mechanisms were proposed to be responsible for such protective effect. The purpose of this study was to explore the effect of the T-cell overexpression of BCL2A1, an anti-apoptotic BCL2 family member without an effect on cell cycle progression, in the development of collagen-induced arthritis. Our results demonstrated an attenuated development of arthritis in these transgenic mice. The protective effect was unrelated to the suppressive activity of regulatory T cells but it was associated with a defective activation of p38 mitogen-activated protein kinase in CD4(+) cells after in vitro TCR stimulation. In addition, the in vitro and in vivo T(H)17 differentiation were impaired in BCL2A1 transgenic mice. Taken together, we demonstrated here a previously unknown role for BCL2A1 controlling the activation of CD4(+) cells and their differentiation into pathogenic proinflammatory T(H)17 cells and identified BCL2A1 as a potential target in the control of autoimmune/inflammatory diseases.
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spelling pubmed-49511112016-08-08 Selective Impairment of T(H)17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes Iglesias, Marcos Augustin, Juan Jesús Alvarez, Pilar Santiuste, Inés Postigo, Jorge Merino, Jesús Merino, Ramón PLoS One Research Article The inhibition of apoptotic cell death in T cells through the dysregulated expression of BCL2 family members has been associated with the protection against the development of different autoimmune diseases. However, multiple mechanisms were proposed to be responsible for such protective effect. The purpose of this study was to explore the effect of the T-cell overexpression of BCL2A1, an anti-apoptotic BCL2 family member without an effect on cell cycle progression, in the development of collagen-induced arthritis. Our results demonstrated an attenuated development of arthritis in these transgenic mice. The protective effect was unrelated to the suppressive activity of regulatory T cells but it was associated with a defective activation of p38 mitogen-activated protein kinase in CD4(+) cells after in vitro TCR stimulation. In addition, the in vitro and in vivo T(H)17 differentiation were impaired in BCL2A1 transgenic mice. Taken together, we demonstrated here a previously unknown role for BCL2A1 controlling the activation of CD4(+) cells and their differentiation into pathogenic proinflammatory T(H)17 cells and identified BCL2A1 as a potential target in the control of autoimmune/inflammatory diseases. Public Library of Science 2016-07-19 /pmc/articles/PMC4951111/ /pubmed/27433938 http://dx.doi.org/10.1371/journal.pone.0159714 Text en © 2016 Iglesias 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
Iglesias, Marcos
Augustin, Juan Jesús
Alvarez, Pilar
Santiuste, Inés
Postigo, Jorge
Merino, Jesús
Merino, Ramón
Selective Impairment of T(H)17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes
title Selective Impairment of T(H)17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes
title_full Selective Impairment of T(H)17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes
title_fullStr Selective Impairment of T(H)17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes
title_full_unstemmed Selective Impairment of T(H)17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes
title_short Selective Impairment of T(H)17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes
title_sort selective impairment of t(h)17-differentiation and protection against autoimmune arthritis after overexpression of bcl2a1 in t lymphocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951111/
https://www.ncbi.nlm.nih.gov/pubmed/27433938
http://dx.doi.org/10.1371/journal.pone.0159714
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