Wilford Goh, Harrison Sudholz, Momeneh Foroutan, Sebastian Scheer, Aline Pfefferle, Rebecca B Delconte, Xiangpeng Meng, Zihan Shen, Robert Hennessey, Isabella Y Kong, Iona S Schuster, Christopher E Andoniou, Melissa J Davis, Soroor Hediyeh-Zadeh, Fernando Souza-Fonseca-Guimaraes, Ian A Parish, Paul Beavis, Daniel Thiele, Michael Chopin, Mariapia A Degli-Esposti, Joe Cursons, Axel Kallies, Jai Rautela, Stephen L Nutt, Nicholas D Huntington
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...
February 2024: Nature Immunology