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The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery
Naive CD4 T cells activated by antigen-presenting cells (APCs) undergo terminal differentiation in the periphery. Multiple mechanisms determine their fates, that is, whether they differentiate into conventional T (Tconv) cells or regulatory T (Treg) cells. The key event during Treg generation is exp...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704186/ https://www.ncbi.nlm.nih.gov/pubmed/29147008 http://dx.doi.org/10.1038/emm.2017.157 |
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author | Lee, Wonyong Kim, Hyeong Su Hwang, Soo Seok Lee, Gap Ryol |
author_facet | Lee, Wonyong Kim, Hyeong Su Hwang, Soo Seok Lee, Gap Ryol |
author_sort | Lee, Wonyong |
collection | PubMed |
description | Naive CD4 T cells activated by antigen-presenting cells (APCs) undergo terminal differentiation in the periphery. Multiple mechanisms determine their fates, that is, whether they differentiate into conventional T (Tconv) cells or regulatory T (Treg) cells. The key event during Treg generation is expression of the transcription factor Foxp3, which is the lineage-determining regulator for Treg differentiation and function. Here we show that the transcription factor Batf3 acts as a fate-decision factor with respect to Tconv versus Tregs by restraining Treg differentiation. Batf3 was preferentially expressed in effector CD4 T cells but not in Treg cells, and ectopic expression of Batf3 inhibited Foxp3 induction. Batf3-deficient CD4 T cells favorably differentiated into Treg cells in vitro and in colonic lamina propria. Batf3 KO mice also showed enhanced Treg function in gut-associated immune disease models (for example, ovalbumin tolerance and inflammatory bowel disease models). Batf3 bound to the CNS1 region of the Foxp3 locus and reduced expression of the gene. Thus, Batf3 is a transcriptional suppressor of Treg differentiation. |
format | Online Article Text |
id | pubmed-5704186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-57041862017-12-07 The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery Lee, Wonyong Kim, Hyeong Su Hwang, Soo Seok Lee, Gap Ryol Exp Mol Med Original Article Naive CD4 T cells activated by antigen-presenting cells (APCs) undergo terminal differentiation in the periphery. Multiple mechanisms determine their fates, that is, whether they differentiate into conventional T (Tconv) cells or regulatory T (Treg) cells. The key event during Treg generation is expression of the transcription factor Foxp3, which is the lineage-determining regulator for Treg differentiation and function. Here we show that the transcription factor Batf3 acts as a fate-decision factor with respect to Tconv versus Tregs by restraining Treg differentiation. Batf3 was preferentially expressed in effector CD4 T cells but not in Treg cells, and ectopic expression of Batf3 inhibited Foxp3 induction. Batf3-deficient CD4 T cells favorably differentiated into Treg cells in vitro and in colonic lamina propria. Batf3 KO mice also showed enhanced Treg function in gut-associated immune disease models (for example, ovalbumin tolerance and inflammatory bowel disease models). Batf3 bound to the CNS1 region of the Foxp3 locus and reduced expression of the gene. Thus, Batf3 is a transcriptional suppressor of Treg differentiation. Nature Publishing Group 2017-11 2017-11-17 /pmc/articles/PMC5704186/ /pubmed/29147008 http://dx.doi.org/10.1038/emm.2017.157 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 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-nc-nd/4.0/ |
spellingShingle | Original Article Lee, Wonyong Kim, Hyeong Su Hwang, Soo Seok Lee, Gap Ryol The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery |
title | The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery |
title_full | The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery |
title_fullStr | The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery |
title_full_unstemmed | The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery |
title_short | The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery |
title_sort | transcription factor batf3 inhibits the differentiation of regulatory t cells in the periphery |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704186/ https://www.ncbi.nlm.nih.gov/pubmed/29147008 http://dx.doi.org/10.1038/emm.2017.157 |
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