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Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses

Author

Listed:
  • Hongkui Xiao

    (Technical University of Denmark (DTU))

  • Isabel Ulmert

    (Technical University of Denmark (DTU))

  • Luisa Bach

    (University of Bonn)

  • Johanna Huber

    (LMU Munich)

  • Hamsa Narasimhan

    (Ludwig-Maximillians-Universität München
    LMU Munich)

  • Ilia Kurochkin

    (Lund University
    Lund University)

  • Yinshui Chang

    (University of Bonn
    LMU Munich)

  • Signe Holst

    (Technical University of Denmark (DTU)
    University of Calgary
    University of Calgary)

  • Urs Mörbe

    (Technical University of Denmark (DTU))

  • Lili Zhang

    (University of Bonn)

  • Andreas Schlitzer

    (University of Bonn)

  • Carlos-Filipe Pereira

    (Lund University
    Lund University
    University of Coimbra)

  • Barbara U. Schraml

    (Ludwig-Maximillians-Universität München
    LMU Munich)

  • Dirk Baumjohann

    (University of Bonn
    LMU Munich)

  • Katharina Lahl

    (Technical University of Denmark (DTU)
    University of Calgary
    University of Calgary
    Lund University)

Abstract

Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 are diminished in the periphery but maintain their ability to cross-present antigen to CD8+ T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDC causes a complete loss of Notch2-dependent cDC2 in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity to Citrobacter rodentium in the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.

Suggested Citation

  • Hongkui Xiao & Isabel Ulmert & Luisa Bach & Johanna Huber & Hamsa Narasimhan & Ilia Kurochkin & Yinshui Chang & Signe Holst & Urs Mörbe & Lili Zhang & Andreas Schlitzer & Carlos-Filipe Pereira & Barba, 2024. "Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46966-6
    DOI: 10.1038/s41467-024-46966-6
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    References listed on IDEAS

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    1. Jesse W. Williams & Melissa Y. Tjota & Bryan S. Clay & Bryan Vander Lugt & Hozefa S. Bandukwala & Cara L. Hrusch & Donna C. Decker & Kelly M. Blaine & Bethany R. Fixsen & Harinder Singh & Roger Sciamm, 2013. "Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation," Nature Communications, Nature, vol. 4(1), pages 1-12, December.
    2. David Sancho & Olivier P. Joffre & Anna M. Keller & Neil C. Rogers & Dolores Martínez & Patricia Hernanz-Falcón & Ian Rosewell & Caetano Reis e Sousa, 2009. "Identification of a dendritic cell receptor that couples sensing of necrosis to immunity," Nature, Nature, vol. 458(7240), pages 899-903, April.
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