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Interferon regulatory factor 1 (IRF-1) promotes intestinal group 3 innate lymphoid responses during Citrobacter rodentium infection

Author

Listed:
  • Angelika Schmalzl

    (Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Tamara Leupold

    (Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Lucas Kreiss

    (Friedrich-Alexander University Erlangen-Nürnberg)

  • Maximilian Waldner

    (Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Sebastian Schürmann

    (Friedrich-Alexander University Erlangen-Nürnberg)

  • Markus F. Neurath

    (Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
    FAU Erlangen-Nürnberg)

  • Christoph Becker

    (Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
    FAU Erlangen-Nürnberg)

  • Stefan Wirtz

    (Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
    FAU Erlangen-Nürnberg)

Abstract

Group 3 innate lymphoid cells (ILC3s) are crucial mediators of immunity and epithelial barrier function during immune responses against extracellular bacteria. Here, we identify Interferon regulatory factor 1 (IRF-1), a transcription factor previously associated with type 1 immunity, as an essential regulator of intestinal ILC3 accumulation and effector cytokine production. We demonstrate that IRF-1 is upregulated in the context of infection with the enteropathogen Citrobacter rodentium and that its presence is central for anatomical containment and prevention of pathogen dissemination. We furthermore show that IRF-1 is required in order for intestinal ILC3s to produce large amounts of the protective effector cytokine IL-22 early in the course of infection. On a molecular level, our data indicate that IRF-1 controls ILC3 numbers and their activation by direct transcriptional regulation of the IL-12Rβ1 chain, thereby allowing ILCs to physiologically respond to IL-23 stimulation.

Suggested Citation

  • Angelika Schmalzl & Tamara Leupold & Lucas Kreiss & Maximilian Waldner & Sebastian Schürmann & Markus F. Neurath & Christoph Becker & Stefan Wirtz, 2022. "Interferon regulatory factor 1 (IRF-1) promotes intestinal group 3 innate lymphoid responses during Citrobacter rodentium infection," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33326-5
    DOI: 10.1038/s41467-022-33326-5
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    1. Jiaqi Yan & Rajendra Bhadane & Meixin Ran & Xiaodong Ma & Yuanqiang Li & Dongdong Zheng & Outi M. H. Salo-Ahen & Hongbo Zhang, 2024. "Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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