Transcription factor T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the RORγt gene

Overactive T(H)17 responses are tightly linked to the development of autoimmunity, yet the factors that negatively regulate differentiation of this lineage remain unknown. Here, we report that T-bet suppresses the development of the T(H)17 cell lineage by inhibiting the transcription of Rorc. T-bet...

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Autores principales: Lazarevic, Vanja, Chen, Xi, Shim, Jae-Hyuck, Hwang, Eun-Sook, Jang, Eunjung, Bolm, Alexandra N., Oukka, Mohamed, Kuchroo, Vijay K., Glimcher, Laurie H.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077962/
https://www.ncbi.nlm.nih.gov/pubmed/21151104
http://dx.doi.org/10.1038/ni.1969
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author Lazarevic, Vanja
Chen, Xi
Shim, Jae-Hyuck
Hwang, Eun-Sook
Jang, Eunjung
Bolm, Alexandra N.
Oukka, Mohamed
Kuchroo, Vijay K.
Glimcher, Laurie H.
author_facet Lazarevic, Vanja
Chen, Xi
Shim, Jae-Hyuck
Hwang, Eun-Sook
Jang, Eunjung
Bolm, Alexandra N.
Oukka, Mohamed
Kuchroo, Vijay K.
Glimcher, Laurie H.
author_sort Lazarevic, Vanja
collection PubMed
description Overactive T(H)17 responses are tightly linked to the development of autoimmunity, yet the factors that negatively regulate differentiation of this lineage remain unknown. Here, we report that T-bet suppresses the development of the T(H)17 cell lineage by inhibiting the transcription of Rorc. T-bet interacts with the transcription factor Runx1 and this interaction blocks Runx1-mediated transactivation of Rorc. T-bet residue Tyr(304) is required for T-bet-Runx1 complex formation, for blocking Runx1 activity and for inhibiting the T(H)17 differentiation program. These data reinforce the concept of master regulators that shape immune responses by simultaneously activating one genetic program while silencing the activity of competing regulators in a common progenitor cell.
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spelling pubmed-30779622011-07-01 Transcription factor T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the RORγt gene Lazarevic, Vanja Chen, Xi Shim, Jae-Hyuck Hwang, Eun-Sook Jang, Eunjung Bolm, Alexandra N. Oukka, Mohamed Kuchroo, Vijay K. Glimcher, Laurie H. Nat Immunol Article Overactive T(H)17 responses are tightly linked to the development of autoimmunity, yet the factors that negatively regulate differentiation of this lineage remain unknown. Here, we report that T-bet suppresses the development of the T(H)17 cell lineage by inhibiting the transcription of Rorc. T-bet interacts with the transcription factor Runx1 and this interaction blocks Runx1-mediated transactivation of Rorc. T-bet residue Tyr(304) is required for T-bet-Runx1 complex formation, for blocking Runx1 activity and for inhibiting the T(H)17 differentiation program. These data reinforce the concept of master regulators that shape immune responses by simultaneously activating one genetic program while silencing the activity of competing regulators in a common progenitor cell. 2010-12-12 2011-01 /pmc/articles/PMC3077962/ /pubmed/21151104 http://dx.doi.org/10.1038/ni.1969 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Lazarevic, Vanja
Chen, Xi
Shim, Jae-Hyuck
Hwang, Eun-Sook
Jang, Eunjung
Bolm, Alexandra N.
Oukka, Mohamed
Kuchroo, Vijay K.
Glimcher, Laurie H.
Transcription factor T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the RORγt gene
title Transcription factor T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the RORγt gene
title_full Transcription factor T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the RORγt gene
title_fullStr Transcription factor T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the RORγt gene
title_full_unstemmed Transcription factor T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the RORγt gene
title_short Transcription factor T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the RORγt gene
title_sort transcription factor t-bet represses t(h)17 differentiation by preventing runx1-mediated activation of the rorγt gene
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077962/
https://www.ncbi.nlm.nih.gov/pubmed/21151104
http://dx.doi.org/10.1038/ni.1969
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