Skip to main content

Unveiling IRF4-steered regulation of context-dependent effector programs in CD4 T cells under Th17- and Treg-skewing conditions.

Cell reports

Authors: 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

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.

Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 40067830

Participating cluster members