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TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells

The mechanisms that underlie the critical dendritic cell (DC) function in maintainance of peripheral immune tolerance are incompletely understood, although the β-catenin signaling pathway is critical for this role. The molecular details by which β-catenin signaling is regulated in DCs are unknown. M...

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Autores principales: Vander Lugt, Bryan, Beck, Zachary T., Fuhlbrigge, Robert C., Hacohen, Nir, Campbell, James J., Boes, Marianne
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098869/
https://www.ncbi.nlm.nih.gov/pubmed/21625453
http://dx.doi.org/10.1371/journal.pone.0020099
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author Vander Lugt, Bryan
Beck, Zachary T.
Fuhlbrigge, Robert C.
Hacohen, Nir
Campbell, James J.
Boes, Marianne
author_facet Vander Lugt, Bryan
Beck, Zachary T.
Fuhlbrigge, Robert C.
Hacohen, Nir
Campbell, James J.
Boes, Marianne
author_sort Vander Lugt, Bryan
collection PubMed
description The mechanisms that underlie the critical dendritic cell (DC) function in maintainance of peripheral immune tolerance are incompletely understood, although the β-catenin signaling pathway is critical for this role. The molecular details by which β-catenin signaling is regulated in DCs are unknown. Mechanical disruption of murine bone marrow-derived DC (BMDC) clusters activates DCs while maintaining their tolerogenic potential and this activation is associated with β-catenin signaling, providing a useful model with which to explore tolerance-associated β-catenin signaling in DCs. In this report, we demonstrate novel molecular features of the signaling events that control DC activation in response to mechanical stimulation. Non-canonical β-catenin signaling is an essential component of this tolerogenic activation and is modulated by adhesion molecules, including integrins. This unique β-catenin-dependent signaling pathway is constitutively active at low levels, suggesting that mechanical stimulation is not necessarily required for induction of this unique activation program. We additionally find that the immunomodulatory cytokine TGF-β antagonizes β-catenin in DCs, thereby selectively suppressing signaling associated with tolerogenic DC activation while having no impact on LPS-induced, β-catenin-independent immunogenic activation. These findings provide new molecular insight into the regulation of a critical signaling pathway for DC function in peripheral immune tolerance.
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spelling pubmed-30988692011-05-27 TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells Vander Lugt, Bryan Beck, Zachary T. Fuhlbrigge, Robert C. Hacohen, Nir Campbell, James J. Boes, Marianne PLoS One Research Article The mechanisms that underlie the critical dendritic cell (DC) function in maintainance of peripheral immune tolerance are incompletely understood, although the β-catenin signaling pathway is critical for this role. The molecular details by which β-catenin signaling is regulated in DCs are unknown. Mechanical disruption of murine bone marrow-derived DC (BMDC) clusters activates DCs while maintaining their tolerogenic potential and this activation is associated with β-catenin signaling, providing a useful model with which to explore tolerance-associated β-catenin signaling in DCs. In this report, we demonstrate novel molecular features of the signaling events that control DC activation in response to mechanical stimulation. Non-canonical β-catenin signaling is an essential component of this tolerogenic activation and is modulated by adhesion molecules, including integrins. This unique β-catenin-dependent signaling pathway is constitutively active at low levels, suggesting that mechanical stimulation is not necessarily required for induction of this unique activation program. We additionally find that the immunomodulatory cytokine TGF-β antagonizes β-catenin in DCs, thereby selectively suppressing signaling associated with tolerogenic DC activation while having no impact on LPS-induced, β-catenin-independent immunogenic activation. These findings provide new molecular insight into the regulation of a critical signaling pathway for DC function in peripheral immune tolerance. Public Library of Science 2011-05-20 /pmc/articles/PMC3098869/ /pubmed/21625453 http://dx.doi.org/10.1371/journal.pone.0020099 Text en Vander Lugt 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Vander Lugt, Bryan
Beck, Zachary T.
Fuhlbrigge, Robert C.
Hacohen, Nir
Campbell, James J.
Boes, Marianne
TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells
title TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells
title_full TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells
title_fullStr TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells
title_full_unstemmed TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells
title_short TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells
title_sort tgf-β suppresses β-catenin-dependent tolerogenic activation program in dendritic cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098869/
https://www.ncbi.nlm.nih.gov/pubmed/21625453
http://dx.doi.org/10.1371/journal.pone.0020099
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