Sequential actions of EOMES and T-BET promote stepwise maturation of natural killer cells

Jiang Zhang, Stéphanie Le Gras, Kevin Pouxvielh, Fabrice Faure, Lucie Fallone, Nicolas Kern, Marion Moreews, Anne-Laure Mathieu, Raphaël Schneider, Quentin Marliac, Mathieu Jung, Aurore Berton, Simon Hayek, Pierre-Olivier Vidalain, Antoine Marçais, Garvin Dodard, Anne Dejean, Laurent Brossay, Yad Ghavi-Helm and Thierry Walzer ()
Additional contact information
Jiang Zhang: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Stéphanie Le Gras: IGBMC, CNRS UMR7104, Inserm U1258, Université de Strasbourg
Kevin Pouxvielh: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Fabrice Faure: Institut NeuroMyoGène, INSERM U1217/CNRS UMR5310, Université de Lyon, Université Claude Bernard
Lucie Fallone: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Nicolas Kern: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Marion Moreews: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Anne-Laure Mathieu: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Raphaël Schneider: Institut de Génomique Fonctionnelle de Lyon, CNRS UMR 5242, Ecole Normale Supérieure de Lyon Université Claude Bernard Lyon 1
Quentin Marliac: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Mathieu Jung: IGBMC, CNRS UMR7104, Inserm U1258, Université de Strasbourg
Aurore Berton: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Simon Hayek: Equipe Chimie et Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS UMR 8601
Pierre-Olivier Vidalain: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Antoine Marçais: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Garvin Dodard: Brown University Alpert Medical School
Anne Dejean: Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), INSERM UMR1291 - CNRS UMR5051 - Université Toulouse III
Laurent Brossay: Brown University Alpert Medical School
Yad Ghavi-Helm: Institut de Génomique Fonctionnelle de Lyon, CNRS UMR 5242, Ecole Normale Supérieure de Lyon Université Claude Bernard Lyon 1
Thierry Walzer: Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract EOMES and T-BET are related T-box transcription factors that control natural killer (NK) cell development. Here we demonstrate that EOMES and T-BET regulate largely distinct gene sets during this process. EOMES is dominantly expressed in immature NK cells and drives early lineage specification by inducing hallmark receptors and functions. By contrast, T-BET is dominant in mature NK cells, where it induces responsiveness to IL-12 and represses the cell cycle, likely through transcriptional repressors. Regardless, many genes with distinct functions are co-regulated by the two transcription factors. By generating two gene-modified mice facilitating chromatin immunoprecipitation of endogenous EOMES and T-BET, we show a strong overlap in their DNA binding targets, as well as extensive epigenetic changes during NK cell differentiation. Our data thus suggest that EOMES and T-BET may distinctly govern, via differential expression and co-factors recruitment, NK cell maturation by inserting partially overlapping epigenetic regulations.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25758-2

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DOI: 10.1038/s41467-021-25758-2

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