Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo.
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 gamma 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.
Kamizono
Shintaro
S
The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Ontario M5G 2C1, Canada.
Duncan
Gordon S
GS
Seidel
Markus G
MG
Morimoto
Akira
A
Hamada
Koichi
K
Grosveld
Gerard
G
Akashi
Koichi
K
Lind
Evan F
EF
Haight
Jillian P
JP
Ohashi
Pamela S
PS
Look
A Thomas
AT
Mak
Tak W
TW
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D007694:Killer Cells, Natural / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D050976:Basic-Leucine Zipper Transcription Factors; C497441:Nfil3 protein, mouse