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Foxp3 Molecular Dynamics in Treg in Juvenile Idiopathic Arthritis

Since the identification of the regulatory T-cell (Treg)-associated transcription factor Foxp3, there have been intensive research efforts to understand its biology and roles in maintaining immune homeostasis. It is well established that thymic selection of a repertoire of self-reactive Foxp3(+) T-c...

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Autores principales: Copland, Alastair, Bending, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175987/
https://www.ncbi.nlm.nih.gov/pubmed/30333832
http://dx.doi.org/10.3389/fimmu.2018.02273
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author Copland, Alastair
Bending, David
author_facet Copland, Alastair
Bending, David
author_sort Copland, Alastair
collection PubMed
description Since the identification of the regulatory T-cell (Treg)-associated transcription factor Foxp3, there have been intensive research efforts to understand its biology and roles in maintaining immune homeostasis. It is well established that thymic selection of a repertoire of self-reactive Foxp3(+) T-cells provides an essential mechanism to minimize reactions to self-antigens in the periphery, and thus aid in the prevention of autoimmunity. It is clear from both genetic and immunological analyses of juvenile idiopathic arthritis (JIA) patients that T-cells have a strong role to play in both the initiation and propagation of disease. The current paradigm is to view autoimmunity as a consequence of an imbalance between inflammatory and immunoregulatory mechanisms. This view has led to the assigning of cells and inflammatory mediators to different classes based on their assumed pro- or anti-inflammatory roles. This is typically reported as ratios of effector T-cells to Treg cells. Problematically, many analyses are based on static “snapshots-in-time,” even though both mouse models and human patient studies have highlighted the dynamic nature of Foxp3(+) T-cells in vivo, which can exhibit plasticity and time-dependent functional states. In this review, we discuss the role of Foxp3 dynamics in the control of T-cell responses in childhood arthritis, by reviewing evidence in humans and relevant mouse models of inflammatory disease. Whilst the cellular dynamics of Treg have been well evaluated—leading to standard data outputs such as frequency, quantity and quality (often assessed by in vitro suppressive capacity)—we discuss how recent insights into the molecular dynamics of Foxp3 transcription and its post-translational control may open up tantalizing new avenues for immunotherapies to treat autoimmune arthritis.
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spelling pubmed-61759872018-10-17 Foxp3 Molecular Dynamics in Treg in Juvenile Idiopathic Arthritis Copland, Alastair Bending, David Front Immunol Immunology Since the identification of the regulatory T-cell (Treg)-associated transcription factor Foxp3, there have been intensive research efforts to understand its biology and roles in maintaining immune homeostasis. It is well established that thymic selection of a repertoire of self-reactive Foxp3(+) T-cells provides an essential mechanism to minimize reactions to self-antigens in the periphery, and thus aid in the prevention of autoimmunity. It is clear from both genetic and immunological analyses of juvenile idiopathic arthritis (JIA) patients that T-cells have a strong role to play in both the initiation and propagation of disease. The current paradigm is to view autoimmunity as a consequence of an imbalance between inflammatory and immunoregulatory mechanisms. This view has led to the assigning of cells and inflammatory mediators to different classes based on their assumed pro- or anti-inflammatory roles. This is typically reported as ratios of effector T-cells to Treg cells. Problematically, many analyses are based on static “snapshots-in-time,” even though both mouse models and human patient studies have highlighted the dynamic nature of Foxp3(+) T-cells in vivo, which can exhibit plasticity and time-dependent functional states. In this review, we discuss the role of Foxp3 dynamics in the control of T-cell responses in childhood arthritis, by reviewing evidence in humans and relevant mouse models of inflammatory disease. Whilst the cellular dynamics of Treg have been well evaluated—leading to standard data outputs such as frequency, quantity and quality (often assessed by in vitro suppressive capacity)—we discuss how recent insights into the molecular dynamics of Foxp3 transcription and its post-translational control may open up tantalizing new avenues for immunotherapies to treat autoimmune arthritis. Frontiers Media S.A. 2018-10-02 /pmc/articles/PMC6175987/ /pubmed/30333832 http://dx.doi.org/10.3389/fimmu.2018.02273 Text en Copyright © 2018 Copland and Bending. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Copland, Alastair
Bending, David
Foxp3 Molecular Dynamics in Treg in Juvenile Idiopathic Arthritis
title Foxp3 Molecular Dynamics in Treg in Juvenile Idiopathic Arthritis
title_full Foxp3 Molecular Dynamics in Treg in Juvenile Idiopathic Arthritis
title_fullStr Foxp3 Molecular Dynamics in Treg in Juvenile Idiopathic Arthritis
title_full_unstemmed Foxp3 Molecular Dynamics in Treg in Juvenile Idiopathic Arthritis
title_short Foxp3 Molecular Dynamics in Treg in Juvenile Idiopathic Arthritis
title_sort foxp3 molecular dynamics in treg in juvenile idiopathic arthritis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175987/
https://www.ncbi.nlm.nih.gov/pubmed/30333832
http://dx.doi.org/10.3389/fimmu.2018.02273
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