Advanced search
1 file | 2.49 MB Add to list

Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection

(2015) JOURNAL OF EXPERIMENTAL MEDICINE. 212(12). p.2015-2025
Author
Organization
Project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) NK cells partially restored a normal maturation, establishing that timely induction of Zeb2 by T-bet is an essential event during NK cell differentiation. Finally, this novel transcriptional cascade could also operate in human as T-bet and Zeb2 are similarly regulated in mouse and human NK cells.
Keywords
EXPRESSION, HOMEOSTASIS, PROTEINS, RECEPTOR, DISEASE, MICE, TRAFFICKING, MOUSE, IN-VIVO

Downloads

  • 2538 15vanHelden.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 2.49 MB

Citation

Please use this url to cite or link to this publication:

MLA
van Helden, Mary et al. “Terminal NK Cell Maturation Is Controlled by Concerted Actions of T-bet and Zeb2 and Is Essential for Melanoma Rejection.” JOURNAL OF EXPERIMENTAL MEDICINE 212.12 (2015): 2015–2025. Print.
APA
van Helden, M., Goossens, S., Daussy, C., Mathieu, A.-L., Faure, F., Marçais, A., Vandamme, N., et al. (2015). Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection. JOURNAL OF EXPERIMENTAL MEDICINE, 212(12), 2015–2025.
Chicago author-date
van Helden, Mary, Steven Goossens, Cécile Daussy, Anne-Laure Mathieu, Fabrice Faure, Antoine Marçais, Niels Vandamme, et al. 2015. “Terminal NK Cell Maturation Is Controlled by Concerted Actions of T-bet and Zeb2 and Is Essential for Melanoma Rejection.” Journal of Experimental Medicine 212 (12): 2015–2025.
Chicago author-date (all authors)
van Helden, Mary, Steven Goossens, Cécile Daussy, Anne-Laure Mathieu, Fabrice Faure, Antoine Marçais, Niels Vandamme, Natalie Farla, Katia Mayol, Sébastien Viel, Sophie Degouve, Emilie Debien, Eve Seuntjens, Andrea Conidi, Julie Chaix, Philippe Mangeot, Simon de Bernard, Laurent Buffat, Jody Haigh, Danny Huylebroeck, Bart Lambrecht, Geert Berx, and Thierry Walzer. 2015. “Terminal NK Cell Maturation Is Controlled by Concerted Actions of T-bet and Zeb2 and Is Essential for Melanoma Rejection.” Journal of Experimental Medicine 212 (12): 2015–2025.
Vancouver
1.
van Helden M, Goossens S, Daussy C, Mathieu A-L, Faure F, Marçais A, et al. Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection. JOURNAL OF EXPERIMENTAL MEDICINE. 2015;212(12):2015–25.
IEEE
[1]
M. van Helden et al., “Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection,” JOURNAL OF EXPERIMENTAL MEDICINE, vol. 212, no. 12, pp. 2015–2025, 2015.
@article{7073554,
  abstract     = {Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) NK cells partially restored a normal maturation, establishing that timely induction of Zeb2 by T-bet is an essential event during NK cell differentiation. Finally, this novel transcriptional cascade could also operate in human as T-bet and Zeb2 are similarly regulated in mouse and human NK cells.},
  author       = {van Helden, Mary and Goossens, Steven and Daussy, Cécile and Mathieu, Anne-Laure and Faure, Fabrice and Marçais, Antoine and Vandamme, Niels and Farla, Natalie and Mayol, Katia and Viel, Sébastien and Degouve, Sophie and Debien, Emilie and Seuntjens, Eve and Conidi, Andrea and Chaix, Julie and Mangeot, Philippe and de Bernard, Simon and Buffat, Laurent and Haigh, Jody and Huylebroeck, Danny and Lambrecht, Bart and Berx, Geert and Walzer, Thierry},
  issn         = {0022-1007},
  journal      = {JOURNAL OF EXPERIMENTAL MEDICINE},
  keywords     = {EXPRESSION,HOMEOSTASIS,PROTEINS,RECEPTOR,DISEASE,MICE,TRAFFICKING,MOUSE,IN-VIVO},
  language     = {eng},
  number       = {12},
  pages        = {2015--2025},
  title        = {Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection},
  url          = {http://dx.doi.org/10.1084/jem.20150809},
  volume       = {212},
  year         = {2015},
}

Altmetric
View in Altmetric
Web of Science
Times cited: