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Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4
FOXP3 is the lineage-defining transcription factor for Tregs, a cell type critical to immune tolerance, but the mechanisms that control FOXP3 expression in Tregs remain incompletely defined, particularly as it relates to signals downstream of TCR and CD28 signaling. Herein, we studied the role of IR...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9452699/ https://www.ncbi.nlm.nih.gov/pubmed/36090981 http://dx.doi.org/10.3389/fimmu.2022.966364 |
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author | Arnold, Preston R. Wen, Mou Zhang, Lei Ying, Yuanlin Xiao, Xiang Chu, Xiufeng Wang, Guangchuan Zhang, Xiaolong Mao, Zhuyun Zhang, Aijun Hamilton, Dale J. Chen, Wenhao Li, Xian C. |
author_facet | Arnold, Preston R. Wen, Mou Zhang, Lei Ying, Yuanlin Xiao, Xiang Chu, Xiufeng Wang, Guangchuan Zhang, Xiaolong Mao, Zhuyun Zhang, Aijun Hamilton, Dale J. Chen, Wenhao Li, Xian C. |
author_sort | Arnold, Preston R. |
collection | PubMed |
description | FOXP3 is the lineage-defining transcription factor for Tregs, a cell type critical to immune tolerance, but the mechanisms that control FOXP3 expression in Tregs remain incompletely defined, particularly as it relates to signals downstream of TCR and CD28 signaling. Herein, we studied the role of IRF4 and BATF3, two transcription factors upregulated upon T cell activation, to the conversion of conventional CD4+ T cells to FOXP3+ T cells (iTregs) in vitro. We found that IRF4 must partner with BATF3 to bind to a regulatory region in the Foxp3 locus where they cooperatively repress FOXP3 expression and iTreg induction. In addition, we found that interactions of these transcription factors are necessary for glycolytic reprogramming of activated T cells that is antagonistic to FOXP3 expression and stability. As a result, Irf4 KO iTregs show increased demethylation of the critical CNS2 region in the Foxp3 locus. Together, our findings provide important insights how BATF3 and IRF4 interactions integrate activating signals to control CD4+ cell fate decisions and govern Foxp3 expression. |
format | Online Article Text |
id | pubmed-9452699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94526992022-09-09 Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4 Arnold, Preston R. Wen, Mou Zhang, Lei Ying, Yuanlin Xiao, Xiang Chu, Xiufeng Wang, Guangchuan Zhang, Xiaolong Mao, Zhuyun Zhang, Aijun Hamilton, Dale J. Chen, Wenhao Li, Xian C. Front Immunol Immunology FOXP3 is the lineage-defining transcription factor for Tregs, a cell type critical to immune tolerance, but the mechanisms that control FOXP3 expression in Tregs remain incompletely defined, particularly as it relates to signals downstream of TCR and CD28 signaling. Herein, we studied the role of IRF4 and BATF3, two transcription factors upregulated upon T cell activation, to the conversion of conventional CD4+ T cells to FOXP3+ T cells (iTregs) in vitro. We found that IRF4 must partner with BATF3 to bind to a regulatory region in the Foxp3 locus where they cooperatively repress FOXP3 expression and iTreg induction. In addition, we found that interactions of these transcription factors are necessary for glycolytic reprogramming of activated T cells that is antagonistic to FOXP3 expression and stability. As a result, Irf4 KO iTregs show increased demethylation of the critical CNS2 region in the Foxp3 locus. Together, our findings provide important insights how BATF3 and IRF4 interactions integrate activating signals to control CD4+ cell fate decisions and govern Foxp3 expression. Frontiers Media S.A. 2022-08-25 /pmc/articles/PMC9452699/ /pubmed/36090981 http://dx.doi.org/10.3389/fimmu.2022.966364 Text en Copyright © 2022 Arnold, Wen, Zhang, Ying, Xiao, Chu, Wang, Zhang, Mao, Zhang, Hamilton, Chen and Li https://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 Arnold, Preston R. Wen, Mou Zhang, Lei Ying, Yuanlin Xiao, Xiang Chu, Xiufeng Wang, Guangchuan Zhang, Xiaolong Mao, Zhuyun Zhang, Aijun Hamilton, Dale J. Chen, Wenhao Li, Xian C. Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4 |
title | Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4 |
title_full | Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4 |
title_fullStr | Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4 |
title_full_unstemmed | Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4 |
title_short | Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4 |
title_sort | suppression of foxp3 expression by the ap-1 family transcription factor batf3 requires partnering with irf4 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9452699/ https://www.ncbi.nlm.nih.gov/pubmed/36090981 http://dx.doi.org/10.3389/fimmu.2022.966364 |
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