Unveiling IRF4-steered regulation of context-dependent effector programs in Th17 and Treg cells

Gabele, A.; Sprang, M.; Cihan, M.; Dietzen, S.; Klein, M.; Harms, G.; Ziesmann, T.; Pape, K.; Wasser, B.; Gomez-Zepeda, D.; Braband, K.; Delacher, M.; Lemmermann, N.; Bittner, S.; Andrade-Navarro, M. A.; Tenzer, S.; Bopp, T.; Distler, U.

doi:10.1101/2023.09.14.557376

bioRxiv · 10.1101/2023.09.14.557376

Unveiling IRF4-steered regulation of context-dependent effector programs in Th17 and Treg cells

Gabele, A.·Sprang, M.·Cihan, M.·Dietzen, S.·Klein, M.·Harms, G.·Ziesmann, T.·Pape, K.·Wasser, B.·Gomez-Zepeda, D.·Braband, K.·Delacher, M.·Lemmermann, N.·Bittner, S.·Andrade-Navarro, M. A.·Tenzer, S.·Bopp, T.·Distler, U.

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Abstract

The transcription factor interferon regulatory factor 4 (IRF4) is crucial for the differentiation and fate determination of pro-inflammatory T helper (Th)17 and the functionally opposing group of immunomodulatory regulatory T (Treg) cells. However, molecular mechanisms of how IRF4 steers diverse transcriptional programs in Th17 and Treg cells are far from being definitive. To unveil IRF4-driven lineage determination in Th17 and Treg cells, we integrated data derived from affinity-purification and full mass spectrometry-based proteome analysis with chromatin immune precipitation sequencing (ChIP-Seq). This allowed the characterization of subtype-specific molecular programs and the identification of novel, previously unknown IRF4 interactors in the Th17/Treg context, such as ROR{gamma}t, AHR, IRF8, BACH2, SATB1, and FLI1. Moreover, our data reveal that most of these transcription factors are recruited to IRF composite elements for the regulation of cell type-specific transcriptional programs providing a valuable resource for studying IRF4-mediated gene regulatory programs in pro- and anti-inflammatory immune responses.

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Gabele, A., Sprang, M., Cihan, M., Dietzen, S., Klein, M., Harms, G., Ziesmann, T., Pape, K., Wasser, B., Gomez-Zepeda, D., Braband, K., Delacher, M., Lemmermann, N., Bittner, S., Andrade-Navarro, M. A., Tenzer, S., Bopp, T., Distler, U.. 2023-09-15. Unveiling IRF4-steered regulation of context-dependent effector programs in Th17 and Treg cells. https://doi.org/10.1101/2023.09.14.557376

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