Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditions
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.
Authors
- Miguel A. Andrade‐Navarro (ORCID: https://orcid.org/0000-0001-6650-1711)
- Ute Distler (ORCID: https://orcid.org/0000-0002-8031-6384)
- Anna Gabele
- Beatrice Wasser
- Tobias Bopp (ORCID: https://orcid.org/0000-0002-3232-8065)
- Gregory S. Harms (ORCID: https://orcid.org/0000-0001-7167-7738)
- Krishnaraj Rajalingam (ORCID: https://orcid.org/0000-0002-4175-9633)
- Stefan Bittner (ORCID: https://orcid.org/0000-0003-2179-3655)
- Kathrin Luise Braband (ORCID: https://orcid.org/0000-0002-7436-1621)
- Maximilian Sprang (ORCID: https://orcid.org/0000-0002-8438-4747)
- Niels A. W. Lemmermann (ORCID: https://orcid.org/0000-0001-9190-6497)
- Katja Luck (ORCID: https://orcid.org/0000-0003-2336-9225)
- Sarah Dietzen
- Stefan Tenzer (ORCID: https://orcid.org/0000-0003-3034-0017)
- Mert Cihan (ORCID: https://orcid.org/0000-0002-7751-3010)
- David Gómez-Zepeda (ORCID: https://orcid.org/0000-0002-9467-1213)
- Tanja Ziesmann (ORCID: https://orcid.org/0009-0009-0399-258X)
- Karolina Romaniuk
- Michael Delacher (ORCID: https://orcid.org/0000-0002-6716-9156)
- Katrin Pape (ORCID: https://orcid.org/0000-0001-9211-5873)
- Georg Bündgen
- Matthias Klein (ORCID: https://orcid.org/0000-0003-1312-1226)
- M Welzel
- Assel Nurbekova (ORCID: https://orcid.org/0009-0000-2106-9179)
- Maxim Emelianov
Institutions
- University of Bonn (DE)
- German Cancer Research Center (DE)
- Johannes Gutenberg University Mainz (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Helmholtz Institute Mainz (DE)
- Novo Nordisk (Germany) (DE)
- DKFZ-ZMBH Alliance (DE)
- Institute of Molecular Biology (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115407
- Citations
- 2
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Deutsche Forschungsgemeinschaft