Cargando…
Transcriptional repressor ZEB2 promotes terminal differentiation of CD8(+) effector and memory T cell populations during infection
ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition–dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicat...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647262/ https://www.ncbi.nlm.nih.gov/pubmed/26503445 http://dx.doi.org/10.1084/jem.20150194 |
_version_ | 1782401062024511488 |
---|---|
author | Omilusik, Kyla D. Best, J. Adam Yu, Bingfei Goossens, Steven Weidemann, Alexander Nguyen, Jessica V. Seuntjens, Eve Stryjewska, Agata Zweier, Christiane Roychoudhuri, Rahul Gattinoni, Luca Bird, Lynne M. Higashi, Yujiro Kondoh, Hisato Huylebroeck, Danny Haigh, Jody Goldrath, Ananda W. |
author_facet | Omilusik, Kyla D. Best, J. Adam Yu, Bingfei Goossens, Steven Weidemann, Alexander Nguyen, Jessica V. Seuntjens, Eve Stryjewska, Agata Zweier, Christiane Roychoudhuri, Rahul Gattinoni, Luca Bird, Lynne M. Higashi, Yujiro Kondoh, Hisato Huylebroeck, Danny Haigh, Jody Goldrath, Ananda W. |
author_sort | Omilusik, Kyla D. |
collection | PubMed |
description | ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition–dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1(hi) effector CD8(+) T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8(+) T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1(hi) effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8(+) T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8(+) T cells. |
format | Online Article Text |
id | pubmed-4647262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-46472622016-05-16 Transcriptional repressor ZEB2 promotes terminal differentiation of CD8(+) effector and memory T cell populations during infection Omilusik, Kyla D. Best, J. Adam Yu, Bingfei Goossens, Steven Weidemann, Alexander Nguyen, Jessica V. Seuntjens, Eve Stryjewska, Agata Zweier, Christiane Roychoudhuri, Rahul Gattinoni, Luca Bird, Lynne M. Higashi, Yujiro Kondoh, Hisato Huylebroeck, Danny Haigh, Jody Goldrath, Ananda W. J Exp Med Research Articles ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition–dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1(hi) effector CD8(+) T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8(+) T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1(hi) effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8(+) T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8(+) T cells. The Rockefeller University Press 2015-11-16 /pmc/articles/PMC4647262/ /pubmed/26503445 http://dx.doi.org/10.1084/jem.20150194 Text en © 2015 Omilusik 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.rupress.org/terms). 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 | Research Articles Omilusik, Kyla D. Best, J. Adam Yu, Bingfei Goossens, Steven Weidemann, Alexander Nguyen, Jessica V. Seuntjens, Eve Stryjewska, Agata Zweier, Christiane Roychoudhuri, Rahul Gattinoni, Luca Bird, Lynne M. Higashi, Yujiro Kondoh, Hisato Huylebroeck, Danny Haigh, Jody Goldrath, Ananda W. Transcriptional repressor ZEB2 promotes terminal differentiation of CD8(+) effector and memory T cell populations during infection |
title | Transcriptional repressor ZEB2 promotes terminal differentiation of CD8(+) effector and memory T cell populations during infection |
title_full | Transcriptional repressor ZEB2 promotes terminal differentiation of CD8(+) effector and memory T cell populations during infection |
title_fullStr | Transcriptional repressor ZEB2 promotes terminal differentiation of CD8(+) effector and memory T cell populations during infection |
title_full_unstemmed | Transcriptional repressor ZEB2 promotes terminal differentiation of CD8(+) effector and memory T cell populations during infection |
title_short | Transcriptional repressor ZEB2 promotes terminal differentiation of CD8(+) effector and memory T cell populations during infection |
title_sort | transcriptional repressor zeb2 promotes terminal differentiation of cd8(+) effector and memory t cell populations during infection |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647262/ https://www.ncbi.nlm.nih.gov/pubmed/26503445 http://dx.doi.org/10.1084/jem.20150194 |
work_keys_str_mv | AT omilusikkylad transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT bestjadam transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT yubingfei transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT goossenssteven transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT weidemannalexander transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT nguyenjessicav transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT seuntjenseve transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT stryjewskaagata transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT zweierchristiane transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT roychoudhurirahul transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT gattinoniluca transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT birdlynnem transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT higashiyujiro transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT kondohhisato transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT huylebroeckdanny transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT haighjody transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection AT goldrathanandaw transcriptionalrepressorzeb2promotesterminaldifferentiationofcd8effectorandmemorytcellpopulationsduringinfection |