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Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4(+) T cell effector functions

Members of the evolutionarily conserved family of the chicken ovalbumin upstream promoter transcription factor NR2F/COUP-TF orphan receptors have been implicated in lymphocyte biology, ranging from activation to differentiation and elicitation of immune effector functions. In particular, a CD4(+) T...

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Autores principales: Hermann-Kleiter, Natascha, Baier, Gottfried
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066320/
https://www.ncbi.nlm.nih.gov/pubmed/24919548
http://dx.doi.org/10.1186/1478-811X-12-38
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author Hermann-Kleiter, Natascha
Baier, Gottfried
author_facet Hermann-Kleiter, Natascha
Baier, Gottfried
author_sort Hermann-Kleiter, Natascha
collection PubMed
description Members of the evolutionarily conserved family of the chicken ovalbumin upstream promoter transcription factor NR2F/COUP-TF orphan receptors have been implicated in lymphocyte biology, ranging from activation to differentiation and elicitation of immune effector functions. In particular, a CD4(+) T cell intrinsic and non-redundant function of NR2F6 as a potent and selective repressor of the transcription of the pro-inflammatory cytokines interleukin (Il) 2, interferon y (ifng) and consequently of T helper (Th)17 CD4(+) T cell-mediated autoimmune disorders has been discovered. NR2F6 serves as an antigen receptor signaling threshold-regulated barrier against autoimmunity where NR2F6 is part of a negative feedback loop that limits inflammatory tissue damage induced by weakly immunogenic antigens such as self-antigens. Under such low affinity antigen receptor stimulation, NR2F6 appears as a prototypical repressor that functions to “lock out” harmful Th17 lineage effector transcription. Mechanistically, only sustained high affinity antigen receptor-induced protein kinase C (PKC)-mediated phosphorylation has been shown to inactivate NR2F6, thereby displacing pre-bound NR2F6 from the DNA and, subsequently, allowing for robust NFAT/AP-1- and RORγt-mediated cytokine transcription. The NR2F6 target gene repertoire thus identifies a general anti-inflammatory gatekeeper role for this orphan receptor. Investigating these signaling pathway(s) will enable a greater knowledge of the genetic, immune, and environmental mechanisms that lead to chronic inflammation and of certain autoimmune disorders in a given individual.
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spelling pubmed-40663202014-06-24 Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4(+) T cell effector functions Hermann-Kleiter, Natascha Baier, Gottfried Cell Commun Signal Review Members of the evolutionarily conserved family of the chicken ovalbumin upstream promoter transcription factor NR2F/COUP-TF orphan receptors have been implicated in lymphocyte biology, ranging from activation to differentiation and elicitation of immune effector functions. In particular, a CD4(+) T cell intrinsic and non-redundant function of NR2F6 as a potent and selective repressor of the transcription of the pro-inflammatory cytokines interleukin (Il) 2, interferon y (ifng) and consequently of T helper (Th)17 CD4(+) T cell-mediated autoimmune disorders has been discovered. NR2F6 serves as an antigen receptor signaling threshold-regulated barrier against autoimmunity where NR2F6 is part of a negative feedback loop that limits inflammatory tissue damage induced by weakly immunogenic antigens such as self-antigens. Under such low affinity antigen receptor stimulation, NR2F6 appears as a prototypical repressor that functions to “lock out” harmful Th17 lineage effector transcription. Mechanistically, only sustained high affinity antigen receptor-induced protein kinase C (PKC)-mediated phosphorylation has been shown to inactivate NR2F6, thereby displacing pre-bound NR2F6 from the DNA and, subsequently, allowing for robust NFAT/AP-1- and RORγt-mediated cytokine transcription. The NR2F6 target gene repertoire thus identifies a general anti-inflammatory gatekeeper role for this orphan receptor. Investigating these signaling pathway(s) will enable a greater knowledge of the genetic, immune, and environmental mechanisms that lead to chronic inflammation and of certain autoimmune disorders in a given individual. BioMed Central 2014-06-12 /pmc/articles/PMC4066320/ /pubmed/24919548 http://dx.doi.org/10.1186/1478-811X-12-38 Text en Copyright © 2014 Hermann-Kleiter and Baier; licensee BioMed Central Ltd. 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 work is properly credited. 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 Review
Hermann-Kleiter, Natascha
Baier, Gottfried
Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4(+) T cell effector functions
title Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4(+) T cell effector functions
title_full Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4(+) T cell effector functions
title_fullStr Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4(+) T cell effector functions
title_full_unstemmed Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4(+) T cell effector functions
title_short Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4(+) T cell effector functions
title_sort orphan nuclear receptor nr2f6 acts as an essential gatekeeper of th17 cd4(+) t cell effector functions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066320/
https://www.ncbi.nlm.nih.gov/pubmed/24919548
http://dx.doi.org/10.1186/1478-811X-12-38
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