Journal Article DKFZ-2025-00546

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

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2025
Cell Press Maryland Heights, MO

Cell reports 44(3), 115407 () [10.1016/j.celrep.2025.115407]
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Abstract: 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.

Keyword(s): CP: Immunology ; ChIP-seq ; FLI1 ; IRF4 ; Th17 cells ; Treg cells ; composite motif ; protein-protein interaction ; proteomics

Classification:

Note: HI-TRON

Contributing Institute(s):
  1. HI-TRON zentral (D190)
  2. Hi-TRON Immunoproteomik (D191)
Research Program(s):
  1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2025
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Medline ; DOAJ ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2025-03-13, last modified 2025-03-16



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