title: Differential requirement for Nfil3 during NK cell development.
abstract: NK cells can be grouped into distinct subsets that are localized to different organs and exhibit a 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 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 or how it induces NK lineage commitment. In this article, we show that Nfil3 is required for the formation of Eomes-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL(+) Eomes(-) NK cells develop independently 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 cells by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia;
authors.forename: Cyril
authors.initials: C
authors.lastname: Seillet
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Huntington
authors.forename: Pradnya
authors.initials: P
authors.lastname: Gangatirkar
authors.forename: Elin
authors.initials: E
authors.lastname: Axelsson
authors.forename: Martina
authors.initials: M
authors.lastname: Minnich
authors.forename: Hugh J M
authors.initials: HJ
authors.lastname: Brady
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Carotta
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C491198:Eomes protein, mouse; C497441:Nfil3 protein, mouse; D020825:T-Box Domain Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand