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The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude

Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constit...

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Autores principales: Li, Zhong-Yin, Morman, Rosemary E., Hegermiller, Emma, Sun, Mengxi, Bartom, Elizabeth T., Maienschein-Cline, Mark, Sigvardsson, Mikael, Kee, Barbara L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056751/
https://www.ncbi.nlm.nih.gov/pubmed/33857289
http://dx.doi.org/10.1084/jem.20202032
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author Li, Zhong-Yin
Morman, Rosemary E.
Hegermiller, Emma
Sun, Mengxi
Bartom, Elizabeth T.
Maienschein-Cline, Mark
Sigvardsson, Mikael
Kee, Barbara L.
author_facet Li, Zhong-Yin
Morman, Rosemary E.
Hegermiller, Emma
Sun, Mengxi
Bartom, Elizabeth T.
Maienschein-Cline, Mark
Sigvardsson, Mikael
Kee, Barbara L.
author_sort Li, Zhong-Yin
collection PubMed
description Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constitutively expressed in NK cells, supports NK cell effector maturation by controlling the amplitude and temporal dynamics of the transcription factor TCF1. TCF1 promotes immature NK cell expansion and restrains differentiation. The increased TCF1 expression in ID2-deficient NK cells arrests their maturation and alters cell surface receptor expression. Moreover, TCF1 limits NK cell functions, such as cytokine-induced IFN-γ production and the ability to clear metastatic melanoma in ID2-deficient NK cells. Our data demonstrate that ID2 sets a threshold for TCF1 during NK cell development, thus controlling the balance of immature and terminally differentiated cells that support future NK cell responses.
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spelling pubmed-80567512021-12-07 The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude Li, Zhong-Yin Morman, Rosemary E. Hegermiller, Emma Sun, Mengxi Bartom, Elizabeth T. Maienschein-Cline, Mark Sigvardsson, Mikael Kee, Barbara L. J Exp Med Article Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constitutively expressed in NK cells, supports NK cell effector maturation by controlling the amplitude and temporal dynamics of the transcription factor TCF1. TCF1 promotes immature NK cell expansion and restrains differentiation. The increased TCF1 expression in ID2-deficient NK cells arrests their maturation and alters cell surface receptor expression. Moreover, TCF1 limits NK cell functions, such as cytokine-induced IFN-γ production and the ability to clear metastatic melanoma in ID2-deficient NK cells. Our data demonstrate that ID2 sets a threshold for TCF1 during NK cell development, thus controlling the balance of immature and terminally differentiated cells that support future NK cell responses. Rockefeller University Press 2021-04-15 /pmc/articles/PMC8056751/ /pubmed/33857289 http://dx.doi.org/10.1084/jem.20202032 Text en © 2021 Li et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Li, Zhong-Yin
Morman, Rosemary E.
Hegermiller, Emma
Sun, Mengxi
Bartom, Elizabeth T.
Maienschein-Cline, Mark
Sigvardsson, Mikael
Kee, Barbara L.
The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude
title The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude
title_full The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude
title_fullStr The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude
title_full_unstemmed The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude
title_short The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude
title_sort transcriptional repressor id2 supports natural killer cell maturation by controlling tcf1 amplitude
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056751/
https://www.ncbi.nlm.nih.gov/pubmed/33857289
http://dx.doi.org/10.1084/jem.20202032
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