Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells
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 cel...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107397/full |
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| author | Kevin Baßler Kevin Baßler Lisa Schmidleithner Mehrnoush Hadaddzadeh Shakiba Tarek Elmzzahi Tarek Elmzzahi Maren Köhne Stefan Floess Rebekka Scholz Naganari Ohkura Timothy Sadlon Kathrin Klee Anna Neubauer Shimon Sakaguchi Simon C. Barry Jochen Huehn Lorenzo Bonaguro Lorenzo Bonaguro Thomas Ulas Thomas Ulas Thomas Ulas Marc Beyer Marc Beyer |
| author_facet | Kevin Baßler Kevin Baßler Lisa Schmidleithner Mehrnoush Hadaddzadeh Shakiba Tarek Elmzzahi Tarek Elmzzahi Maren Köhne Stefan Floess Rebekka Scholz Naganari Ohkura Timothy Sadlon Kathrin Klee Anna Neubauer Shimon Sakaguchi Simon C. Barry Jochen Huehn Lorenzo Bonaguro Lorenzo Bonaguro Thomas Ulas Thomas Ulas Thomas Ulas Marc Beyer Marc Beyer |
| author_sort | Kevin Baßler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T21:58:39Z |
| format | Article |
| id | doaj.art-08e3960cd2734ae4aaeb37de7e1fb8d2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T21:58:39Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-08e3960cd2734ae4aaeb37de7e1fb8d22023-07-25T11:11:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.11073971107397Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cellsKevin Baßler0Kevin Baßler1Lisa Schmidleithner2Mehrnoush Hadaddzadeh Shakiba3Tarek Elmzzahi4Tarek Elmzzahi5Maren Köhne6Stefan Floess7Rebekka Scholz8Naganari Ohkura9Timothy Sadlon10Kathrin Klee11Anna Neubauer12Shimon Sakaguchi13Simon C. Barry14Jochen Huehn15Lorenzo Bonaguro16Lorenzo Bonaguro17Thomas Ulas18Thomas Ulas19Thomas Ulas20Marc Beyer21Marc Beyer22Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyLIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, GermanyImmunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyImmunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyImmunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, AustraliaImmunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyExperimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyImmunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyLaboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanMolecular Immunology, Robinson Research Institute, University of Adelaide, Norwich Centre, North Adelaide, SA, AustraliaLIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, GermanyImmunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyLaboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanMolecular Immunology, Robinson Research Institute, University of Adelaide, Norwich Centre, North Adelaide, SA, AustraliaExperimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanySystems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyLIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, GermanySystems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyLIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, GermanyPRECISE, Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, GermanyImmunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyPRECISE, Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, GermanyCD4+ 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107397/fullTreg cellsMEOX1Foxp3regulatory T cellshuman CD4 |
| spellingShingle | Kevin Baßler Kevin Baßler Lisa Schmidleithner Mehrnoush Hadaddzadeh Shakiba Tarek Elmzzahi Tarek Elmzzahi Maren Köhne Stefan Floess Rebekka Scholz Naganari Ohkura Timothy Sadlon Kathrin Klee Anna Neubauer Shimon Sakaguchi Simon C. Barry Jochen Huehn Lorenzo Bonaguro Lorenzo Bonaguro Thomas Ulas Thomas Ulas Thomas Ulas Marc Beyer Marc Beyer Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells Frontiers in Immunology Treg cells MEOX1 Foxp3 regulatory T cells human CD4 |
| title | Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells |
| title_full | Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells |
| title_fullStr | Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells |
| title_full_unstemmed | Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells |
| title_short | Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells |
| title_sort | identification of the novel foxp3 dependent treg cell transcription factor meox1 by high dimensional analysis of human cd4 t cells |
| topic | Treg cells MEOX1 Foxp3 regulatory T cells human CD4 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107397/full |
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