| First Author | Miyake T | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 41 | Pages | 17680-5 |
| PubMed ID | 20876105 | Mgi Jnum | J:165405 |
| Mgi Id | MGI:4837271 | Doi | 10.1073/pnas.1012977107 |
| Citation | Miyake T, et al. (2010) IkappaBzeta is essential for natural killer cell activation in response to IL-12 and IL-18. Proc Natl Acad Sci U S A 107(41):17680-5 |
| abstractText | IkappaBzeta, encoded by Nfibiz, is a nuclear IkappaB-like protein harboring ankyrin repeats. IkappaBzeta has been shown to regulate IL-6 production in macrophages and Th17 development in T cells. However, the role of IkappaBzeta in natural killer (NK) cells has not be understood. In the present study, we found that the expression of IkappaBzeta was rapidly induced in response to IL-18 in NK cells, but not in T cells. Analysis of Nfkbiz(-/-) mice revealed that IkappaBzeta was essential for the production of IFN-gamma 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. IkappaBzeta was recruited on the proximal promoter region of the Ifng gene, and overexpression of IkappaBzeta together with IL-12 activated the Ifng promoter. Furthermore, Nfkbiz(-/-) mice were highly susceptible to mouse MCMV infection. Taken together, these results demonstrate that IkappaBzeta is essential for the activation of NK cells and antiviral host defense responses. |
