I?B? is essential for natural killer cell activation in response to IL-12 and IL-18.

ABSTRACT: I?B?, encoded by Nfibiz, is a nuclear I?B-like protein harboring ankyrin repeats. I?B? has been shown to regulate IL-6 production in macrophages and Th17 development in T cells. However, the role of I?B? in natural killer (NK) cells has not be understood. In the present study, we found that the expression of I?B? was rapidly induced in response to IL-18 in NK cells, but not in T cells. Analysis of Nfkbiz(-/-) mice revealed that I?B? was essential for the production of IFN-? 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. I?B? was recruited on the proximal promoter region of the Ifng gene, and overexpression of I?B? together with IL-12 activated the Ifng promoter. Furthermore, Nfkbiz(-/-) mice were highly susceptible to mouse MCMV infection. Taken together, these results demonstrate that I?B? is essential for the activation of NK cells and antiviral host defense responses.

SUBMITTER: Miyake T 

PROVIDER: S-EPMC2955119 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature