Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo

Shintaro Kamizono, Gordon S. Duncan, Markus G. Seidel, Akira Morimoto, Koichi Hamada, Gerard Grosveld, Koichi Akashi, Evan F. Lind, Jillian P. Haight, Pamela S. Ohashi, A. Thomas Look, Tak W. Mak

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221 Citations (Scopus)


Nuclear factor interleukin-3 (Nfil3; also known as E4-binding protein 4) is a basic region leucine zipper transcription factor that has antiapoptotic activity in vitro under conditions of growth factor withdrawal. To study the role of Nfil3 in vivo, we generated gene-targeted Nfil3-deficient (Nfil3 -/-) mice. Nfil3-/- mice were born at normal Mendelian frequency and were grossly normal and fertile. Although numbers of T cells, B cells, and natural killer (NK) T cells were normal in Nfil3-/- mice, a specific disruption in NK cell development resulted in severely reduced numbers of mature NK cells in the periphery. This defect was NK cell intrinsic in nature, leading to a failure to reject MHC class I-deficient cells in vivo and reductions in both interferon γ production and cytolytic activity in vitro. Our results confirm the specific and essential requirement of Nfil3 for the development of cells of the NK lineage.

Original languageEnglish
Pages (from-to)2977-2986
Number of pages10
JournalJournal of Experimental Medicine
Issue number13
Publication statusPublished - Dec 21 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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