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https://hdl.handle.net/2440/140521
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Type: | Journal article |
Title: | IKAROS and AIOLOS directly regulate AP-1 transcriptional complexes and are essential for NK cell development |
Author: | Goh, W. Sudholz, H. Foroutan, M. Scheer, S. Pfefferle, A. Delconte, R.B. Meng, X. Shen, Z. Hennessey, R. Kong, I.Y. Schuster, I.S. Andoniou, C.E. Davis, M.J. Hediyeh-Zadeh, S. Souza-Fonseca-Guimaraes, F. Parish, I.A. Beavis, P. Thiele, D. Chopin, M. Degli-Esposti, M.A. et al. |
Citation: | Nature Immunology, 2024; 25(2):240-255 |
Publisher: | Nature Research |
Issue Date: | 2024 |
ISSN: | 1529-2908 1529-2908 |
Statement of Responsibility: | Wilford Goh ... Zihan Shen ... Melissa J. Davis ... et al. |
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. |
Keywords: | Innate lymphoid cells; Interleukins |
Rights: | © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
DOI: | 10.1038/s41590-023-01718-4 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/GNT1124784 http://purl.org/au-research/grants/nhmrc/GNT1066770 http://purl.org/au-research/grants/nhmrc/GNT1057852 http://purl.org/au-research/grants/nhmrc/GNT1124907 http://purl.org/au-research/grants/nhmrc/GNT1057812 http://purl.org/au-research/grants/nhmrc/GNT1049407 http://purl.org/au-research/grants/nhmrc/GNT1027472 http://purl.org/au-research/grants/nhmrc/GNT1184615 http://purl.org/au-research/grants/nhmrc/GNT1195296 http://purl.org/au-research/grants/nhmrc/GNT1155342 http://purl.org/au-research/grants/nhmrc/GNT1119298 |
Published version: | http://dx.doi.org/10.1038/s41590-023-01718-4 |
Appears in Collections: | Research Outputs |
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