Attenuation of TCR-induced transcription by Bach2 controls regulatory T cell differentiation and homeostasis
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Liao, Yang
Garnham, Alexandra L
Vasanthakumar, Ajithkumar
Gloury, Renee
Blume, Jonas
Teh, Peggy P
Chisanga, David
Thelemann, Christoph
Rivera, Fabian de Labastida
Engwerda, Christian R
Corcoran, Lynn
Kometani, Kohei
Kurosaki, Tomohiro
et al.
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Abstract
Differentiation and homeostasis of Foxp3+ regulatory T (Treg) cells are strictly controlled by T-cell receptor (TCR) signals; however, molecular mechanisms that govern these processes are incompletely understood. Here we show that Bach2 is an important regulator of Treg cell differentiation and homeostasis downstream of TCR signaling. Bach2 prevents premature differentiation of fully suppressive effector Treg (eTreg) cells, limits IL-10 production and is required for the development of peripherally induced Treg (pTreg) cells in the gastrointestinal tract. Bach2 attenuates TCR signaling-induced IRF4-dependent Treg cell differentiation. Deletion of IRF4 promotes inducible Treg cell differentiation and rescues pTreg cell differentiation in the absence of Bach2. In turn, loss of Bach2 normalizes eTreg cell differentiation of IRF4-deficient Treg cells. Mechanistically, Bach2 counteracts the DNA-binding activity of IRF4 and limits chromatin accessibility, thereby attenuating IRF4-dependent transcription. Thus, Bach2 balances TCR signaling induced transcriptional activity of IRF4 to maintain homeostasis of thymically-derived and peripherally-derived Treg cells.
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Nature Communications
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11
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1
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© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Biological sciences
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
FACTOR IRF4
DNA-METHYLATION
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Sidwell, T; Liao, Y; Garnham, AL; Vasanthakumar, A; Gloury, R; Blume, J; Teh, PP; Chisanga, D; Thelemann, C; Rivera, FDL; Engwerda, CR; Corcoran, L; Kometani, K; Kurosaki, T; et al., Attenuation of TCR-induced transcription by Bach2 controls regulatory T cell differentiation and homeostasis, NATURE COMMUNICATIONS, 2020, 11 (1), pp. 252:1-252:17