IKAROS and AIOLOS directly regulate AP-1 transcriptional complexes and are essential for NK cell development

Goh, W; Sudholz, H; Foroutan, M; Scheer, S; Pfefferle, A; Delconte, RB; Meng, X; Shen, Z; Hennessey, R; Kong, IY; Schuster, IS; Andoniou, CE; Davis, MJ; Hediyeh-Zadeh, S; Souza-Fonseca-Guimaraes, F; Parish, IA; Beavis, P; Thiele, D; Chopin, M; Degli-Esposti, MA; Cursons, J; Kallies, A; Rautela, J; Nutt, SL; Huntington, ND

Author(s): Goh, W; Sudholz, H; Foroutan, M; Scheer, S; Pfefferle, A; Delconte, RB; Meng, X; Shen, Z; Hennessey, R; Kong, IY; Schuster, IS; Andoniou, CE; Davis, MJ; Hediyeh-Zadeh, S; Souza-Fonseca-Guimaraes, F; Parish, IA; Beavis, P; Thiele, D; Chopin, M; Degli-Esposti, MA; Cursons, J; Kallies, A; Rautela, J; Nutt, SL; Huntington, ND;
Details: Publication Year 2024-01-05,Volume 25,Issue #2,Page 240-255
Journal Title: Nature Immunology
Abstract: Ikaros transcription factors are essential for adaptive lymphocyte function, yet their role in innate lymphopoiesis is unknown. Using conditional genetic inactivation, we show that Ikzf1/Ikaros is essential for normal natural killer (NK) cell lymphopoiesis and IKZF1 directly represses Cish, a negative regulator of interleukin-15 receptor resulting in impaired interleukin-15 receptor signaling. Both Bcl2l11 and BIM levels, and intrinsic apoptosis were increased in Ikzf1-null NK cells, which in part accounts for NK lymphopenia as both were restored to normal levels when Ikzf1 and Bcl2l11 were co-deleted. Ikzf1-null NK cells presented extensive transcriptional alterations with reduced AP-1 transcriptional complex expression and increased expression of Ikzf2/Helios and Ikzf3/Aiolos. IKZF1 and IKZF3 directly bound AP-1 family members and deletion of both Ikzf1 and Ikzf3 in NK cells resulted in further reductions in Jun/Fos expression and complete loss of peripheral NK cells. Collectively, we show that Ikaros family members are important regulators of apoptosis, cytokine responsiveness and AP-1 transcriptional activity.
Publisher: NPG
Keywords: *Transcription Factor AP-1/genetics; *Killer Cells, Natural/metabolism; Receptors, Interleukin-15; Ikaros Transcription Factor/genetics/metabolism
Research Division(s): Inflammation; Bioinformatics; Immunology; Bioinformatics; Immunology
PubMed ID: 38182668
Publisher's Version: https://doi.org/10.1038/s41590-023-01718-4
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-01-25 09:17:59

Last Modified: 2024-03-11 09:39:15