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Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3(+) inducible regulatory T cells

Forkhead box P3 (FOXP3)(+)CD4(+)CD25(+) inducible regulatory T (iT reg) cells play an important role in immune tolerance and homeostasis. In this study, we show that the transforming growth factor-β (TGF-β) induces the expression of the Runt-related transcription factors RUNX1 and RUNX3 in CD4(+) T...

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Autores principales: Klunker, Sven, Chong, Mark M.W., Mantel, Pierre-Yves, Palomares, Oscar, Bassin, Claudio, Ziegler, Mario, Rückert, Beate, Meiler, Flurina, Akdis, Mübeccel, Littman, Dan R., Akdis, Cezmi A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806624/
https://www.ncbi.nlm.nih.gov/pubmed/19917773
http://dx.doi.org/10.1084/jem.20090596
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author Klunker, Sven
Chong, Mark M.W.
Mantel, Pierre-Yves
Palomares, Oscar
Bassin, Claudio
Ziegler, Mario
Rückert, Beate
Meiler, Flurina
Akdis, Mübeccel
Littman, Dan R.
Akdis, Cezmi A.
author_facet Klunker, Sven
Chong, Mark M.W.
Mantel, Pierre-Yves
Palomares, Oscar
Bassin, Claudio
Ziegler, Mario
Rückert, Beate
Meiler, Flurina
Akdis, Mübeccel
Littman, Dan R.
Akdis, Cezmi A.
author_sort Klunker, Sven
collection PubMed
description Forkhead box P3 (FOXP3)(+)CD4(+)CD25(+) inducible regulatory T (iT reg) cells play an important role in immune tolerance and homeostasis. In this study, we show that the transforming growth factor-β (TGF-β) induces the expression of the Runt-related transcription factors RUNX1 and RUNX3 in CD4(+) T cells. This induction seems to be a prerequisite for the binding of RUNX1 and RUNX3 to three putative RUNX binding sites in the FOXP3 promoter. Inactivation of the gene encoding RUNX cofactor core-binding factor-β (CBFβ) in mice and small interfering RNA (siRNA)-mediated suppression of RUNX1 and RUNX3 in human T cells resulted in reduced expression of Foxp3. The in vivo conversion of naive CD4(+) T cells into Foxp3(+) iT reg cells was significantly decreased in adoptively transferred Cbfb(F/F) CD4-cre naive T cells into Rag2(−/−) mice. Both RUNX1 and RUNX3 siRNA silenced human T reg cells and Cbfb(F/F) CD4-cre mouse T reg cells showed diminished suppressive function in vitro. Circulating human CD4(+) CD25(high) CD127(−) T reg cells significantly expressed higher levels of RUNX3, FOXP3, and TGF-β mRNA compared with CD4(+)CD25(−) cells. Furthermore, FOXP3 and RUNX3 were colocalized in human tonsil T reg cells. These data demonstrate Runx transcription factors as a molecular link in TGF-β–induced Foxp3 expression in iT reg cell differentiation and function.
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spelling pubmed-28066242010-05-23 Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3(+) inducible regulatory T cells Klunker, Sven Chong, Mark M.W. Mantel, Pierre-Yves Palomares, Oscar Bassin, Claudio Ziegler, Mario Rückert, Beate Meiler, Flurina Akdis, Mübeccel Littman, Dan R. Akdis, Cezmi A. J Exp Med Article Forkhead box P3 (FOXP3)(+)CD4(+)CD25(+) inducible regulatory T (iT reg) cells play an important role in immune tolerance and homeostasis. In this study, we show that the transforming growth factor-β (TGF-β) induces the expression of the Runt-related transcription factors RUNX1 and RUNX3 in CD4(+) T cells. This induction seems to be a prerequisite for the binding of RUNX1 and RUNX3 to three putative RUNX binding sites in the FOXP3 promoter. Inactivation of the gene encoding RUNX cofactor core-binding factor-β (CBFβ) in mice and small interfering RNA (siRNA)-mediated suppression of RUNX1 and RUNX3 in human T cells resulted in reduced expression of Foxp3. The in vivo conversion of naive CD4(+) T cells into Foxp3(+) iT reg cells was significantly decreased in adoptively transferred Cbfb(F/F) CD4-cre naive T cells into Rag2(−/−) mice. Both RUNX1 and RUNX3 siRNA silenced human T reg cells and Cbfb(F/F) CD4-cre mouse T reg cells showed diminished suppressive function in vitro. Circulating human CD4(+) CD25(high) CD127(−) T reg cells significantly expressed higher levels of RUNX3, FOXP3, and TGF-β mRNA compared with CD4(+)CD25(−) cells. Furthermore, FOXP3 and RUNX3 were colocalized in human tonsil T reg cells. These data demonstrate Runx transcription factors as a molecular link in TGF-β–induced Foxp3 expression in iT reg cell differentiation and function. The Rockefeller University Press 2009-11-23 /pmc/articles/PMC2806624/ /pubmed/19917773 http://dx.doi.org/10.1084/jem.20090596 Text en © 2009 Klunker et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Klunker, Sven
Chong, Mark M.W.
Mantel, Pierre-Yves
Palomares, Oscar
Bassin, Claudio
Ziegler, Mario
Rückert, Beate
Meiler, Flurina
Akdis, Mübeccel
Littman, Dan R.
Akdis, Cezmi A.
Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3(+) inducible regulatory T cells
title Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3(+) inducible regulatory T cells
title_full Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3(+) inducible regulatory T cells
title_fullStr Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3(+) inducible regulatory T cells
title_full_unstemmed Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3(+) inducible regulatory T cells
title_short Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3(+) inducible regulatory T cells
title_sort transcription factors runx1 and runx3 in the induction and suppressive function of foxp3(+) inducible regulatory t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806624/
https://www.ncbi.nlm.nih.gov/pubmed/19917773
http://dx.doi.org/10.1084/jem.20090596
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