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

Zhong Yin Li, Rosemary E. Morman, Emma Hegermiller, Mengxi Sun, Elizabeth T. Bartom, Mark Maienschein-Cline, Mikael Sigvardsson, Barbara L. Kee

Research output: Contribution to journalArticlepeer-review

7 Citations (SciVal)

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 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.

Original languageEnglish
Article numbere20202032
JournalJournal of Experimental Medicine
Volume218
Issue number6
DOIs
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Cell and Molecular Biology

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