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Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis

Author

Listed:
  • Franziska Herster

    (University of Tübingen)

  • Zsofia Bittner

    (University of Tübingen)

  • Nathan K. Archer

    (Johns Hopkins University School of Medicine)

  • Sabine Dickhöfer

    (University of Tübingen)

  • David Eisel

    (University of Tübingen
    David Eisel, BioNTech)

  • Tatjana Eigenbrod

    (University Hospital Heidelberg)

  • Thomas Knorpp

    (NMI Natural and Medical Sciences Institute at the University of Tübingen)

  • Nicole Schneiderhan-Marra

    (NMI Natural and Medical Sciences Institute at the University of Tübingen)

  • Markus W. Löffler

    (University of Tübingen
    University Hospital Tübingen
    University Hospital Tübingen)

  • Hubert Kalbacher

    (Interfaculty Institute of Biochemistry, University of Tübingen)

  • Tim Vierbuchen

    (Research Group Innate Immunity, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Deutsches Zentrum für Lungenforschung (DZL))

  • Holger Heine

    (Research Group Innate Immunity, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Deutsches Zentrum für Lungenforschung (DZL))

  • Lloyd S. Miller

    (Johns Hopkins University School of Medicine)

  • Dominik Hartl

    (University Children’s Hospital and Interdisciplinary Center for Infectious Diseases, University of Tübingen
    Novartis Institutes for BioMedical Research (NIBR))

  • Lukas Freund

    (University Hospital Heidelberg)

  • Knut Schäkel

    (University Hospital Heidelberg)

  • Martin Heister

    (University Hospital Tübingen)

  • Kamran Ghoreschi

    (University Hospital Tübingen
    Department of Dermatology, Charité – Universitätsmedizin Berlin)

  • Alexander N. R. Weber

    (University of Tübingen)

Abstract

Psoriasis is an inflammatory skin disease with strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37. LL37 in complex with DNA and RNA is thought to initiate disease exacerbation via plasmacytoid dendritic cells. However, the source of nucleic acids supposed to start this initial inflammatory event remains unknown. We show here that primary murine and human PMNs mount a fulminant and self-propagating neutrophil extracellular trap (NET) and cytokine response, but independently of the canonical NET component, DNA. Unexpectedly, RNA, which is abundant in NETs and psoriatic but not healthy skin, in complex with LL37 triggered TLR8/TLR13-mediated cytokine and NET release by PMNs in vitro and in vivo. Transfer of NETs to naive human PMNs prompts additional NET release, promoting further inflammation. Our study thus uncovers a self-propagating vicious cycle contributing to chronic inflammation in psoriasis, and NET-associated RNA (naRNA) as a physiologically relevant NET component.

Suggested Citation

  • Franziska Herster & Zsofia Bittner & Nathan K. Archer & Sabine Dickhöfer & David Eisel & Tatjana Eigenbrod & Thomas Knorpp & Nicole Schneiderhan-Marra & Markus W. Löffler & Hubert Kalbacher & Tim Vier, 2020. "Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13756-4
    DOI: 10.1038/s41467-019-13756-4
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