Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditions
Summary: The transcription factor interferon regulatory factor 4 (IRF4) is crucial for the fate determination of pro-inflammatory T helper (Th) 17 and the functionally opposing group of immunomodulatory regulatory T (Treg) cells. However, the molecular mechanisms of how IRF4 steers diverse transcrip...
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Elsevier
2025-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725001780 |
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| author | Anna Gabele Maximilian Sprang Mert Cihan Mareen Welzel Assel Nurbekova Karolina Romaniuk Sarah Dietzen Matthias Klein Georg Bündgen Maxim Emelianov Gregory Harms Krishnaraj Rajalingam Tanja Ziesmann Katrin Pape Beatrice Wasser David Gomez-Zepeda Kathrin Braband Michael Delacher Niels Lemmermann Stefan Bittner Miguel A. Andrade-Navarro Stefan Tenzer Katja Luck Tobias Bopp Ute Distler |
| author_facet | Anna Gabele Maximilian Sprang Mert Cihan Mareen Welzel Assel Nurbekova Karolina Romaniuk Sarah Dietzen Matthias Klein Georg Bündgen Maxim Emelianov Gregory Harms Krishnaraj Rajalingam Tanja Ziesmann Katrin Pape Beatrice Wasser David Gomez-Zepeda Kathrin Braband Michael Delacher Niels Lemmermann Stefan Bittner Miguel A. Andrade-Navarro Stefan Tenzer Katja Luck Tobias Bopp Ute Distler |
| author_sort | Anna Gabele |
| collection | DOAJ |
| description | Summary: The transcription factor interferon regulatory factor 4 (IRF4) is crucial for the fate determination of pro-inflammatory T helper (Th) 17 and the functionally opposing group of immunomodulatory regulatory T (Treg) cells. However, the molecular mechanisms of how IRF4 steers diverse transcriptional programs in Th17 and Treg cells are far from being definitive. Here, we integrated data derived from affinity-purification and full mass-spectrometry-based proteome analysis with chromatin immunoprecipitation sequencing. This allowed the characterization of subtype-specific molecular programs and the identification of IRF4 interactors in the Th17/Treg context. Our data reveal that IRF4-interacting transcription factors are recruited to IRF composite elements for the regulation of cell-type-specific transcriptional programs as exemplarily demonstrated for FLI1, which, in cooperation with IRF4, promotes Th17-specific gene expression. FLI1 inhibition markedly impaired Th17 differentiation. The present “omics” dataset provides a valuable resource for studying IRF4-mediated gene regulatory programs in pro- and anti-inflammatory immune responses. |
| format | Article |
| id | doaj-art-0a6417b547fa46be9b0bb285c9e5057d |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-0a6417b547fa46be9b0bb285c9e5057d2025-08-20T01:58:00ZengElsevierCell Reports2211-12472025-03-0144311540710.1016/j.celrep.2025.115407Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditionsAnna Gabele0Maximilian Sprang1Mert Cihan2Mareen Welzel3Assel Nurbekova4Karolina Romaniuk5Sarah Dietzen6Matthias Klein7Georg Bündgen8Maxim Emelianov9Gregory Harms10Krishnaraj Rajalingam11Tanja Ziesmann12Katrin Pape13Beatrice Wasser14David Gomez-Zepeda15Kathrin Braband16Michael Delacher17Niels Lemmermann18Stefan Bittner19Miguel A. Andrade-Navarro20Stefan Tenzer21Katja Luck22Tobias Bopp23Ute Distler24Institute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyFaculty of Biology, Johannes Gutenberg University Mainz, 55128 Mainz, GermanyFaculty of Biology, Johannes Gutenberg University Mainz, 55128 Mainz, GermanyInstitute of Molecular Biology gGmbH, 55128 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Novo Nordisk Pharma GmbH, 55124 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyResearch Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Cell Biology Unit, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyResearch Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Cell Biology Unit, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyDepartment of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyDepartment of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyHelmholtz Institute for Translational Oncology, 55131 Mainz, Germany; Deutsches Krebsforschungszentrum, 69120 Heidelberg, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyResearch Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Institute for Virology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Institute of Virology, Medical Faculty, University Bonn, 53127 Bonn, GermanyResearch Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyFaculty of Biology, Johannes Gutenberg University Mainz, 55128 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Helmholtz Institute for Translational Oncology, 55131 Mainz, Germany; Deutsches Krebsforschungszentrum, 69120 Heidelberg, GermanyInstitute of Molecular Biology gGmbH, 55128 Mainz, GermanyInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Corresponding authorInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; Corresponding authorSummary: The transcription factor interferon regulatory factor 4 (IRF4) is crucial for the fate determination of pro-inflammatory T helper (Th) 17 and the functionally opposing group of immunomodulatory regulatory T (Treg) cells. However, the molecular mechanisms of how IRF4 steers diverse transcriptional programs in Th17 and Treg cells are far from being definitive. Here, we integrated data derived from affinity-purification and full mass-spectrometry-based proteome analysis with chromatin immunoprecipitation sequencing. This allowed the characterization of subtype-specific molecular programs and the identification of IRF4 interactors in the Th17/Treg context. Our data reveal that IRF4-interacting transcription factors are recruited to IRF composite elements for the regulation of cell-type-specific transcriptional programs as exemplarily demonstrated for FLI1, which, in cooperation with IRF4, promotes Th17-specific gene expression. FLI1 inhibition markedly impaired Th17 differentiation. The present “omics” dataset provides a valuable resource for studying IRF4-mediated gene regulatory programs in pro- and anti-inflammatory immune responses.http://www.sciencedirect.com/science/article/pii/S2211124725001780CP: Immunology |
| spellingShingle | Anna Gabele Maximilian Sprang Mert Cihan Mareen Welzel Assel Nurbekova Karolina Romaniuk Sarah Dietzen Matthias Klein Georg Bündgen Maxim Emelianov Gregory Harms Krishnaraj Rajalingam Tanja Ziesmann Katrin Pape Beatrice Wasser David Gomez-Zepeda Kathrin Braband Michael Delacher Niels Lemmermann Stefan Bittner Miguel A. Andrade-Navarro Stefan Tenzer Katja Luck Tobias Bopp Ute Distler Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditions Cell Reports CP: Immunology |
| title | Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditions |
| title_full | Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditions |
| title_fullStr | Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditions |
| title_full_unstemmed | Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditions |
| title_short | Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditions |
| title_sort | unveiling irf4 steered regulation of context dependent effector programs in cd4 t cells under th17 and treg skewing conditions |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725001780 |
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