TY - JOUR
T1 - The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude
AU - Li, Zhong Yin
AU - Morman, Rosemary E.
AU - Hegermiller, Emma
AU - Sun, Mengxi
AU - Bartom, Elizabeth T.
AU - Maienschein-Cline, Mark
AU - Sigvardsson, Mikael
AU - Kee, Barbara L.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1084/jem.20202032
DO - 10.1084/jem.20202032
M3 - Article
C2 - 33857289
AN - SCOPUS:85104328484
SN - 0022-1007
VL - 218
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
M1 - e20202032
ER -