IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-09683-z.html
   My bibliography  Save this article

CXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-α production in systemic sclerosis

Author

Listed:
  • Roberto Lande

    (Istituto Superiore di Sanità (ISS))

  • Ernest Y. Lee

    (University of California)

  • Raffaella Palazzo

    (Istituto Superiore di Sanità (ISS))

  • Barbara Marinari

    (University of Tor Vergata)

  • Immacolata Pietraforte

    (Istituto Superiore di Sanità)

  • Giancarlo Santiago Santos

    (University of California)

  • Yves Mattenberger

    (University of Geneva)

  • Francesca Spadaro

    (Confocal Microscopy Unit, Core Facilities)

  • Katia Stefanantoni

    (University La Sapienza)

  • Nicoletta Iannace

    (University La Sapienza)

  • Aleksandra Maria Dufour

    (University Hospital and School of Medicine)

  • Mario Falchi

    (National AIDS Center)

  • Manuela Bianco

    (Istituto Superiore di Sanità (ISS))

  • Elisabetta Botti

    (University of Tor Vergata)

  • Luca Bianchi

    (University of Tor Vergata)

  • Montserrat Alvarez

    (University Hospital and School of Medicine)

  • Valeria Riccieri

    (University La Sapienza)

  • Marie-Elise Truchetet

    (University Hospital)

  • Gerard C.L. Wong

    (University of California)

  • Carlo Chizzolini

    (University Hospital and School of Medicine)

  • Loredana Frasca

    (Istituto Superiore di Sanità (ISS)
    University Hospital and School of Medicine)

Abstract

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis and vasculopathy. CXCL4 represents an early serum biomarker of severe SSc and likely contributes to inflammation via chemokine signaling pathways, but the exact role of CXCL4 in SSc pathogenesis is unclear. Here, we elucidate an unanticipated mechanism for CXCL4-mediated immune amplification in SSc, in which CXCL4 organizes “self” and microbial DNA into liquid crystalline immune complexes that amplify TLR9-mediated plasmacytoid dendritic cell (pDC)-hyperactivation and interferon-α production. Surprisingly, this activity does not require CXCR3, the CXCL4 receptor. Importantly, we find that CXCL4-DNA complexes are present in vivo and correlate with type I interferon (IFN-I) in SSc blood, and that CXCL4-positive skin pDCs coexpress IFN-I-related genes. Thus, we establish a direct link between CXCL4 overexpression and the IFN-I-gene signature in SSc and outline a paradigm in which chemokines can drastically modulate innate immune receptors without being direct agonists.

Suggested Citation

  • Roberto Lande & Ernest Y. Lee & Raffaella Palazzo & Barbara Marinari & Immacolata Pietraforte & Giancarlo Santiago Santos & Yves Mattenberger & Francesca Spadaro & Katia Stefanantoni & Nicoletta Ianna, 2019. "CXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-α production in systemic sclerosis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09683-z
    DOI: 10.1038/s41467-019-09683-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-09683-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-09683-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Chao Yang & Mahesh Bachu & Yong Du & Caroline Brauner & Ruoxi Yuan & Marie Dominique Ah Kioon & Giancarlo Chesi & Franck J. Barrat & Lionel B. Ivashkiv, 2022. "CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09683-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.