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

Abstract

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.

A Distal Enhancer in Il12b Is the Target of Transcriptional Repression by the STAT3 Pathway and Requires the Basic Leucine Zipper (B-ZIP) Protein NFIL3

“…5B). Because NK cells are absent in the NFIL3-deficient mice (30,46), it is important to note that these experiments do not necessarily indicate that the increase in IL-12p40 alone is the cause of disease in these mice. Further experiments with conditional Nfil3 knockout mice will be necessary to establish the cell-specific contributions of NFIL3 to the overall immune response to T. gondii.…”

Intracellular osteopontin regulates homeostasis and function of natural killer cells

“…Developmental and survival signals downstream of the IL-15 receptor (IL-15R) in NK cells are thought to be mediated, in part, by the basic leucine zipper transcription factor (TF) Nfil3 (nuclear factor interleukin-3 regulated; also known as E4BP4) (10,11). However, whereas expression of Nfil3 is essential for early development of NK cells, survival and homeostasis of mature NK cells is Nfil3 independent (12).…”

Recruitment of Histone Methyltransferase G9a Mediates Transcriptional Repression of Fgf21 Gene by E4BP4 Protein*

“…In E4bp4 knockout mice, it has been shown that E4BP4 is critical for NK cell development and IgE expression in B cells (12)(13)(14). In addition to its role in the immune system, E4bp4 is also highly expressed in the liver, adipose tissue, and the suprachiasmatic nuclei of the hypothalamus (15).…”