Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection
Omilusik KD, Best JA, Yu B, Goossens S, Weidemann A, Nguyen JV, Seuntjens E, Stryjewska A, Zweier C, Roychoudhuri R, Gattinoni L, Bird LM, Higashi Y, Kondoh H, Huylebroeck D, Haigh J, Goldrath AW (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 212
Pages Range: 2027-39
Journal Issue: 12
DOI: 10.1084/jem.20150194
Abstract
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.
Authors with CRIS profile
Alexander Weidemann
Department of Medicine 4 – Nephrology and Hypertension
Christiane Zweier
Lehrstuhl für Humangenetik
Involved external institutions
University of California, San Diego
United States (USA) (US)
Monash University
Australia (AU)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
Kyoto Sangyo University / 京都産業大学
Japan (JP)
Aichi Human Service Center
Japan (JP)
National Cancer Institute (NCI)
United States (USA) (US)
United States (USA) (US)
Monash University
Australia (AU)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
Kyoto Sangyo University / 京都産業大学
Japan (JP)
Aichi Human Service Center
Japan (JP)
National Cancer Institute (NCI)
United States (USA) (US)
How to cite
APA:
Omilusik, K.D., Best, J.A., Yu, B., Goossens, S., Weidemann, A., Nguyen, J.V.,... Goldrath, A.W. (2015). Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection. Journal of Experimental Medicine, 212(12), 2027-39. https://dx.doi.org/10.1084/jem.20150194
MLA:
Omilusik, Kyla D., et al. "Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection." Journal of Experimental Medicine 212.12 (2015): 2027-39.
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