Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells

Frontiers in Immunology

Immunology

Stefan Floess¹  Jochen Huehn¹  Lisa Schmidleithner²  Anna Neubauer²  Mehrnoush Hadaddzadeh Shakiba²  Rebekka Scholz²  Maren Köhne²  Tarek Elmzzahi³  Marc Beyer⁴  Kathrin Klee⁵  Naganari Ohkura⁶  Shimon Sakaguchi⁶  Simon C. Barry⁷  Timothy Sadlon⁷  Lorenzo Bonaguro⁸  Kevin Baßler⁸  Thomas Ulas⁹ 

[1] Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany;Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany;Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany;Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia;Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany;PRECISE, Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany;LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, Germany;Laboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan;Molecular Immunology, Robinson Research Institute, University of Adelaide, Norwich Centre, North Adelaide, SA, Australia;Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany;LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, Germany;Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany;LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, Germany;PRECISE, Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany;

关键词: Treg cells;    MEOX1;    Foxp3;    regulatory T cells;    human CD4;   

DOI  :  10.3389/fimmu.2023.1107397

 received in 2022-11-24, accepted in 2023-06-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

CD4+ T cells play a central role in the adaptive immune response through their capacity to activate, support and control other immune cells. Although these cells have become the focus of intense research, a comprehensive understanding of the underlying regulatory networks that orchestrate CD4+ T cell function and activation is still incomplete. Here, we analyzed a large transcriptomic dataset consisting of 48 different human CD4+ T cell conditions. By performing reverse network engineering, we identified six common denominators of CD4+ T cell functionality (CREB1, E2F3, AHR, STAT1, NFAT5 and NFATC3). Moreover, we also analyzed condition-specific genes which led us to the identification of the transcription factor MEOX1 in Treg cells. Expression of MEOX1 was comparable to FOXP3 in Treg cells and can be upregulated by IL-2. Epigenetic analyses revealed a permissive epigenetic landscape for MEOX1 solely in Treg cells. Knockdown of MEOX1 in Treg cells revealed a profound impact on downstream gene expression programs and Treg cell suppressive capacity. These findings in the context of CD4+ T cells contribute to a better understanding of the transcriptional networks and biological mechanisms controlling CD4+ T cell functionality, which opens new avenues for future therapeutic strategies.

【 授权许可】

Unknown   
Copyright © 2023 Baßler, Schmidleithner, Shakiba, Elmzzahi, Köhne, Floess, Scholz, Ohkura, Sadlon, Klee, Neubauer, Sakaguchi, Barry, Huehn, Bonaguro, Ulas and Beyer