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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.
Afiliación
  • Omilusik KD; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
  • Best JA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
  • Yu B; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
  • Goossens S; Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, 9052
  • Weidemann A; Department of Nephrology and Hypertension, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
  • Nguyen JV; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
  • Seuntjens E; Laboratory of Molecular Biology (Celgen), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium.
  • Stryjewska A; Laboratory of Molecular Biology (Celgen), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium.
  • Zweier C; Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
  • Roychoudhuri R; Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
  • Gattinoni L; Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
  • Bird LM; Department of Pediatrics, Rady Children's Hospital San Diego, University of California, San Diego, La Jolla, CA 92093.
  • Higashi Y; Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan.
  • Kondoh H; Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan.
  • Huylebroeck D; Laboratory of Molecular Biology (Celgen), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium Department of Cell Biology, Erasmus MC, 3015 CN Rotterdam, Netherlands.
  • Haigh J; Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia.
  • Goldrath AW; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093 agoldrath@ucsd.edu.
J Exp Med ; 212(12): 2027-39, 2015 Nov 16.
Article en En | MEDLINE | ID: mdl-26503445
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Subgrupos de Linfocitos T / Proteínas de Homeodominio / Linfocitos T CD8-positivos / Coriomeningitis Linfocítica Límite: Animals / Humans / Male Idioma: En Revista: J Exp Med Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Subgrupos de Linfocitos T / Proteínas de Homeodominio / Linfocitos T CD8-positivos / Coriomeningitis Linfocítica Límite: Animals / Humans / Male Idioma: En Revista: J Exp Med Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos