Project description:Natural killer (NK) cells can be grouped into distinct subsets that are localized to different organs and exhibit different capacity to secrete cytokines and mediate cytotoxicity. Despite these hallmarks that reflect tissue-specific specialization in NK cells, little is known about the factors that control the development of these distinct subsets. The basic leucine zipper transcription factor nuclear factor interleukin 3 (Nfil3; E4bp4) is essential for bone marrow-derived NK cell development but it is not clear whether Nfil3 is equally important for all NK cell subsets nor how it induces NK lineage commitment. Here we show that Nfil3 is required for the formation of Eomesodermin (Eomes)-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL+ Eomes- NK cells develop independent of Nfil3. Loss of Nfil3 during the development of bone marrow-derived NK cells resulted in reduced expression of Eomes and, conversely, restoration of Eomes expression in Nfil3-/- progenitors rescued NK cell development and maturation. Collectively, these findings demonstrate that Nfil3 drives the formation of mature NK cell by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3. RNA-sequencing of natural killer (NK) cell subsets
Project description:Natural killer (NK) cells can be grouped into distinct subsets that are localized to different organs and exhibit different capacity to secrete cytokines and mediate cytotoxicity. Despite these hallmarks that reflect tissue-specific specialization in NK cells, little is known about the factors that control the development of these distinct subsets. The basic leucine zipper transcription factor nuclear factor interleukin 3 (Nfil3; E4bp4) is essential for bone marrow-derived NK cell development but it is not clear whether Nfil3 is equally important for all NK cell subsets nor how it induces NK lineage commitment. Here we show that Nfil3 is required for the formation of Eomesodermin (Eomes)-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL+ Eomes- NK cells develop independent of Nfil3. Loss of Nfil3 during the development of bone marrow-derived NK cells resulted in reduced expression of Eomes and, conversely, restoration of Eomes expression in Nfil3-/- progenitors rescued NK cell development and maturation. Collectively, these findings demonstrate that Nfil3 drives the formation of mature NK cell by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3.
Project description:Nfil3 has multiple functions during conventional NK cell and thymic NK cell development. Nfil3 controls NK cell development from the earliest committed NK cell progenitor stage. Nfil3-/- prepro NK cells retained T-cell potential due to the failure to repress T cell specific genes. At later stages of NK cell development, Nfil3 regulates the formation of mature NK cells by promoting directly or indirectly the expression of transcription factor Eomes. We also demonstrate that Nfil3 is important for thymic NK cell development whereas Trail+ immature NK cells generated in the bone marrow of neonates and in the adult liver develop independent of Nfil3 function. We used microarrays to analyse the changes in gene expression due to the presence or absence of Nfil3, both in prepro NK cells and ALP cells (all lymphoid progenitors) Samples were obtained on two experimentation dates. Replicate 1 was processed in April 2012, replicate 2 was processed in May 2012.
Project description:Nfil3 has multiple functions during conventional NK cell and thymic NK cell development. Nfil3 controls NK cell development from the earliest committed NK cell progenitor stage. Nfil3-/- prepro NK cells retained T-cell potential due to the failure to repress T cell specific genes. At later stages of NK cell development, Nfil3 regulates the formation of mature NK cells by promoting directly or indirectly the expression of transcription factor Eomes. We also demonstrate that Nfil3 is important for thymic NK cell development whereas Trail+ immature NK cells generated in the bone marrow of neonates and in the adult liver develop independent of Nfil3 function. We used microarrays to analyse the changes in gene expression due to the presence or absence of Nfil3, both in prepro NK cells and ALP cells (all lymphoid progenitors)