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A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

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Published on: November 2, 2018

IκBζ is essential for natural killer cell activation in response to IL-12 and IL-18

Tohru Miyake1, Takashi Satoh, Hiroki Kato

  • 1Laboratory of Host Defense, Laboratory of Systems Immunology, WPI Immunology Frontier Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|September 30, 2010
PubMed

IκBζ, encoded by Nfibiz, is a nuclear IκB-like protein harboring ankyrin repeats. IκBζ has been shown to regulate IL-6 production in macrophages and Th17 development in T cells. However, the role of IκBζ in natural killer (NK) cells has not be understood. In the present study, we found that the expression of IκBζ was rapidly induced in response to IL-18 in NK cells, but not in T cells. Analysis of Nfkbiz(-/-) mice revealed that IκBζ was essential for the production of IFN-γ production and cytotoxic activity in NK cells in response to IL-12 and/or IL-18 stimulation. IL-12/IL-18-mediated gene induction was profoundly impaired in Nfkbiz(-/-) NK cells. Whereas the phosphorylation of STAT4 was normally induced by IL-12 stimulation, STAT4 was not recruited to the Ifng gene regions in Nfkbiz(-/-) NK cells. Acetylation of histone 3 K9 on Ifng regions was also abrogated in Nfkbiz(-/-) NK cells. IκBζ was recruited on the proximal promoter region of the Ifng gene, and overexpression of IκBζ together with IL-12 activated the Ifng promoter. Furthermore, Nfkbiz(-/-) mice were highly susceptible to mouse MCMV infection. Taken together, these results demonstrate that IκBζ is essential for the activation of NK cells and antiviral host defense responses.

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