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Publication : Zeb2 regulates differentiation of long-lived effector of invariant natural killer T cells.

First Author  Iyoda T Year  2023
Journal  Commun Biol Volume  6
Issue  1 Pages  1070
PubMed ID  37903859 Mgi Jnum  J:342234
Mgi Id  MGI:7545928 Doi  10.1038/s42003-023-05421-w
Citation  Iyoda T, et al. (2023) Zeb2 regulates differentiation of long-lived effector of invariant natural killer T cells. Commun Biol 6(1):1070
abstractText  After activation, some invariant natural killer T (iNKT) cells are differentiated into Klrg1(+) long-lived effector NKT1 cells. However, the regulation from the effector phase to the memory phase has not been elucidated. Zeb2 is a zinc finger E homeobox-binding transcription factor and is expressed in a variety of immune cells, but its function in iNKT cell differentiation remains also unknown. Here, we show that Zeb2 is dispensable for development of iNKT cells in the thymus and their maintenance in steady state peripheral tissues. After ligand stimulation, Zeb2 plays essential roles in the differentiation to and maintenance of Klrg1(+) Cx3cr1(+)GzmA(+) iNKT cell population derived from the NKT1 subset. Our results including single-cell-RNA-seq analysis indicate that Zeb2 regulates Klrg1(+) long-lived iNKT cell differentiation by preventing apoptosis. Collectively, this study reveals the crucial transcriptional regulation by Zeb2 in establishment of the memory iNKT phase through driving differentiation of Klrg1(+) Cx3cr1(+)GzmA(+) iNKT population.
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