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

Autor: Baßler K; Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, Germany., Schmidleithner L; Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany., Shakiba MH; Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany., Elmzzahi T; 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., Köhne M; Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany., Floess S; Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany., Scholz R; Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany., Ohkura N; Laboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan., Sadlon T; Molecular Immunology, Robinson Research Institute, University of Adelaide, Norwich Centre, North Adelaide, SA, Australia., Klee K; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, Germany., Neubauer A; Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany., Sakaguchi S; Laboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan., Barry SC; Molecular Immunology, Robinson Research Institute, University of Adelaide, Norwich Centre, North Adelaide, SA, Australia., Huehn J; Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany., Bonaguro L; Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, Germany., Ulas T; 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., Beyer M; 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.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2023 Jul 25; Vol. 14, pp. 1107397. Date of Electronic Publication: 2023 Jul 25 (Print Publication: 2023).
DOI: 10.3389/fimmu.2023.1107397
Abstrakt: 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 T reg cells. Expression of MEOX1 was comparable to FOXP3 in T reg cells and can be upregulated by IL-2. Epigenetic analyses revealed a permissive epigenetic landscape for MEOX1 solely in T reg cells. Knockdown of MEOX1 in T reg cells revealed a profound impact on downstream gene expression programs and T reg 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Baßler, Schmidleithner, Shakiba, Elmzzahi, Köhne, Floess, Scholz, Ohkura, Sadlon, Klee, Neubauer, Sakaguchi, Barry, Huehn, Bonaguro, Ulas and Beyer.)
Databáze: MEDLINE
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