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Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts

Author

Listed:
  • Nicolaj S. Hackert

    (Heidelberg University Hospital
    Heidelberg University Hospital
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Felix A. Radtke

    (Heidelberg University Hospital
    Heidelberg University Hospital
    Brigham and Women’s Hospital, Harvard Medical School
    University of Oxford)

  • Tarik Exner

    (Heidelberg University Hospital
    Heidelberg University Hospital)

  • Hanns-Martin Lorenz

    (Heidelberg University Hospital)

  • Carsten Müller-Tidow

    (Heidelberg University Hospital
    University of Heidelberg)

  • Peter A. Nigrovic

    (Harvard Medical School
    Brigham and Women’s Hospital, Harvard Medical School)

  • Guido Wabnitz

    (Heidelberg University Hospital)

  • Ricardo Grieshaber-Bouyer

    (Heidelberg University Hospital
    Heidelberg University Hospital
    University of Heidelberg
    Friedrich Alexander Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen)

Abstract

Neutrophils are frequently studied in mouse models, but the extent to which findings translate to humans remains poorly defined. In an integrative analysis of 11 mouse and 13 human datasets, we find a strong correlation of neutrophil gene expression across species. In inflammation, neutrophils display substantial transcriptional diversity but share a core inflammation program. This program includes genes encoding IL-1 family members, CD14, IL-4R, CD69, and PD-L1. Chromatin accessibility of core inflammation genes increases in blood compared to bone marrow and further in tissue. Transcription factor enrichment analysis implicates members of the NF-κB family and AP-1 complex as important drivers, and HoxB8 neutrophils with JunB knockout show a reduced expression of core inflammation genes in resting and activated cells. In independent single-cell validation data, neutrophil activation by type I or type II interferon, G-CSF, and E. coli leads to upregulation in core inflammation genes. In COVID-19 patients, higher expression of core inflammation genes in neutrophils is associated with more severe disease. In vitro treatment with GM-CSF, LPS, and type II interferon induces surface protein upregulation of core inflammation members. Together, we demonstrate transcriptional conservation in neutrophils in homeostasis and identify a core inflammation program shared across heterogeneous inflammatory conditions.

Suggested Citation

  • Nicolaj S. Hackert & Felix A. Radtke & Tarik Exner & Hanns-Martin Lorenz & Carsten Müller-Tidow & Peter A. Nigrovic & Guido Wabnitz & Ricardo Grieshaber-Bouyer, 2023. "Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43573-9
    DOI: 10.1038/s41467-023-43573-9
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