YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity

Regulatory T (T(reg)) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for T(reg)-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in T(reg) ce...

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Autores principales: Hwang, Soo Seok, Jang, Sung Woong, Kim, Min Kyung, Kim, Lark Kyun, Kim, Bong-Sung, Kim, Hyeong Su, Kim, Kiwan, Lee, Wonyong, Flavell, Richard A., Lee, Gap Ryol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762897/
https://www.ncbi.nlm.nih.gov/pubmed/26892542
http://dx.doi.org/10.1038/ncomms10789
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author Hwang, Soo Seok
Jang, Sung Woong
Kim, Min Kyung
Kim, Lark Kyun
Kim, Bong-Sung
Kim, Hyeong Su
Kim, Kiwan
Lee, Wonyong
Flavell, Richard A.
Lee, Gap Ryol
author_facet Hwang, Soo Seok
Jang, Sung Woong
Kim, Min Kyung
Kim, Lark Kyun
Kim, Bong-Sung
Kim, Hyeong Su
Kim, Kiwan
Lee, Wonyong
Flavell, Richard A.
Lee, Gap Ryol
author_sort Hwang, Soo Seok
collection PubMed
description Regulatory T (T(reg)) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for T(reg)-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in T(reg) cells than T(conv) cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of T(reg) cells. YY1 is increased in T(reg) cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of T(reg) cells by blocking Foxp3.
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spelling pubmed-47628972016-03-04 YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity Hwang, Soo Seok Jang, Sung Woong Kim, Min Kyung Kim, Lark Kyun Kim, Bong-Sung Kim, Hyeong Su Kim, Kiwan Lee, Wonyong Flavell, Richard A. Lee, Gap Ryol Nat Commun Article Regulatory T (T(reg)) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for T(reg)-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in T(reg) cells than T(conv) cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of T(reg) cells. YY1 is increased in T(reg) cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of T(reg) cells by blocking Foxp3. Nature Publishing Group 2016-02-19 /pmc/articles/PMC4762897/ /pubmed/26892542 http://dx.doi.org/10.1038/ncomms10789 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Hwang, Soo Seok
Jang, Sung Woong
Kim, Min Kyung
Kim, Lark Kyun
Kim, Bong-Sung
Kim, Hyeong Su
Kim, Kiwan
Lee, Wonyong
Flavell, Richard A.
Lee, Gap Ryol
YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity
title YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity
title_full YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity
title_fullStr YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity
title_full_unstemmed YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity
title_short YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity
title_sort yy1 inhibits differentiation and function of regulatory t cells by blocking foxp3 expression and activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762897/
https://www.ncbi.nlm.nih.gov/pubmed/26892542
http://dx.doi.org/10.1038/ncomms10789
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