T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow. 2014

Cécile Daussy, and Fabrice Faure, and Katia Mayol, and Sébastien Viel, and Georg Gasteiger, and Emily Charrier, and Jacques Bienvenu, and Thomas Henry, and Emilie Debien, and Uzma A Hasan, and Jacqueline Marvel, and Keigyou Yoh, and Satoru Takahashi, and Immo Prinz, and Simon de Bernard, and Laurent Buffat, and Thierry Walzer
CIRI, International Center for Infectiology Research, Université de Lyon; 2 Institut National de la Santé et de la Recherche Médicale, U1111; 3 Ecole Normale Supérieure de Lyon; 4 Université Lyon 1, Centre International de Recherche en Infectiologie; and 5 Centre National de la Recherche Scientifique, UMR5308, 69007 Lyon, France.

Trail(+)DX5(-)Eomes(-) natural killer (NK) cells arise in the mouse fetal liver and persist in the adult liver. Their relationships with Trail(-)DX5(+) NK cells remain controversial. We generated a novel Eomes-GFP reporter murine model to address this question. We found that Eomes(-) NK cells are not precursors of classical Eomes(+) NK cells but rather constitute a distinct lineage of innate lymphoid cells. Eomes(-) NK cells are strictly dependent on both T-bet and IL-15, similarly to NKT cells. We observed that, in the liver, expression of T-bet in progenitors represses Eomes expression and the development of Eomes(+) NK cells. Reciprocally, the bone marrow (BM) microenvironment restricts T-bet expression in developing NK cells. Ectopic expression of T-bet forces the development of Eomes(-) NK cells, demonstrating that repression of T-bet is essential for the development of Eomes(+) NK cells. Gene profile analyses show that Eomes(-) NK cells share part of their transcriptional program with NKT cells, including genes involved in liver homing and NK cell receptors. Moreover, Eomes(-) NK cells produce a broad range of cytokines, including IL-2 and TNF in vitro and in vivo, during immune responses against vaccinia virus. Thus, mutually exclusive expression of T-bet and Eomes drives the development of different NK cell lineages with complementary functions.

UI MeSH Term Description Entries
D007694 Killer Cells, Natural Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type. NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D046228 Microarray Analysis The simultaneous analysis, on a microchip, of multiple samples or targets arranged in an array format. Microarray Analytical Devices,Microarray Microchips,Nanoarray Analytical Devices,Analysis, Microarray,Analytical Device, Microarray,Analytical Device, Nanoarray,Analytical Devices, Microarray,Analytical Devices, Nanoarray,Device, Microarray Analytical,Device, Nanoarray Analytical,Devices, Microarray Analytical,Devices, Nanoarray Analytical,Microarray Analytical Device,Microarray Microchip,Microchip, Microarray,Microchips, Microarray,Nanoarray Analytical Device
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D055153 Stem Cell Niche A particular zone of tissue composed of a specialized microenvironment where stem cells are retained in a undifferentiated, self-renewable state. Stem Cell Microenvironment,Cell Microenvironment, Stem,Cell Microenvironments, Stem,Cell Niche, Stem,Cell Niches, Stem,Microenvironment, Stem Cell,Microenvironments, Stem Cell,Niche, Stem Cell,Niches, Stem Cell,Stem Cell Microenvironments,Stem Cell Niches
D055879 Gene Knock-In Techniques Techniques used to add in exogenous gene sequence such as mutated genes; REPORTER GENES, to study mechanisms of gene expression; or regulatory control sequences, to study effects of temporal changes to GENE EXPRESSION. Gene Knock In,Gene Knock In Techniques,Gene Knock-In,Gene Knock Ins,Gene Knock-In Technique,Gene Knock-Ins,In, Gene Knock,Ins, Gene Knock,Knock In, Gene,Knock Ins, Gene,Knock-In Technique, Gene,Knock-In Techniques, Gene,Knock-In, Gene,Knock-Ins, Gene,Technique, Gene Knock-In,Techniques, Gene Knock-In

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