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, 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.

doi:10.1038/s41590-023-01718-4

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

Date

2024

Authors

Goh, W.

Sudholz, H.

Foroutan, M.

Scheer, S.

Pfefferle, A.

Delconte, R.B.

Meng, X.

Shen, Z.

Hennessey, R.

Kong, I.Y.

Type:

Journal article

Citation

Nature Immunology, 2024; 25(2):240-255

Statement of Responsibility

Wilford Goh ... Zihan Shen ... Melissa J. Davis ... et al.

DOI

10.1038/s41590-023-01718-4

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.

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.

Grant ID

Published Version

http://dx.doi.org/10.1038/s41590-023-01718-4

Persistent link to this record

https://hdl.handle.net/2440/140521

Full item page

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

Date

Authors

Editors

Advisors

Journal Title

Journal ISSN

Volume Title

Type:

Citation

Statement of Responsibility

Conference Name

DOI

Abstract

School/Discipline

Dissertation Note

Provenance

Description

Access Status

Rights

License

Grant ID

Published Version

Call number

Persistent link to this record