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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 LU and Kee, Barbara L. (2021) In Journal of Experimental Medicine 218(6).
Abstract

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... (More)

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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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
218
issue
6
article number
e20202032
publisher
Rockefeller University Press
external identifiers
  • scopus:85104328484
  • pmid:33857289
ISSN
0022-1007
DOI
10.1084/jem.20202032
language
English
LU publication?
yes
id
e6ade786-ac8b-48ac-9197-ed50ae92d03e
date added to LUP
2021-04-26 09:28:55
date last changed
2025-01-13 07:21:11
@article{e6ade786-ac8b-48ac-9197-ed50ae92d03e,
  abstract     = {{<p>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.</p>}},
  author       = {{Li, Zhong Yin and Morman, Rosemary E. and Hegermiller, Emma and Sun, Mengxi and Bartom, Elizabeth T. and Maienschein-Cline, Mark and Sigvardsson, Mikael and Kee, Barbara L.}},
  issn         = {{0022-1007}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Journal of Experimental Medicine}},
  title        = {{The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude}},
  url          = {{http://dx.doi.org/10.1084/jem.20202032}},
  doi          = {{10.1084/jem.20202032}},
  volume       = {{218}},
  year         = {{2021}},
}