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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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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. |
format | Online Article Text |
id | pubmed-8056751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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