TY - JOUR
AU - Gabele, Anna
AU - Sprang, Maximilian
AU - Cihan, Mert
AU - Welzel, Mareen
AU - Nurbekova, Assel
AU - Romaniuk, Karolina
AU - Dietzen, Sarah
AU - Klein, Matthias
AU - Bündgen, Georg
AU - Emelianov, Maxim
AU - Harms, Gregory
AU - Rajalingam, Krishnaraj
AU - Ziesmann, Tanja
AU - Pape, Katrin
AU - Wasser, Beatrice
AU - Gomez-Zepeda, David
AU - Braband, Kathrin
AU - Delacher, Michael
AU - Lemmermann, Niels
AU - Bittner, Stefan
AU - Andrade-Navarro, Miguel A
AU - Tenzer, Stefan
AU - Luck, Katja
AU - Bopp, Tobias
AU - Distler, Ute
TI - Unveiling IRF4-steered regulation of context-dependent effector programs in CD4+ T cells under Th17- and Treg-skewing conditions.
JO - Cell reports
VL - 44
IS - 3
SN - 2211-1247
CY - Maryland Heights, MO
PB - Cell Press
M1 - DKFZ-2025-00546
SP - 115407
PY - 2025
N1 - HI-TRON
AB - 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.
KW - CP: Immunology (Other)
KW - ChIP-seq (Other)
KW - FLI1 (Other)
KW - IRF4 (Other)
KW - Th17 cells (Other)
KW - Treg cells (Other)
KW - composite motif (Other)
KW - protein-protein interaction (Other)
KW - proteomics (Other)
LB - PUB:(DE-HGF)16
C6 - pmid:40067830
DO - DOI:10.1016/j.celrep.2025.115407
UR - https://inrepo02.dkfz.de/record/299791
ER -