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

Roberto Lande (), Ernest Y. Lee, Raffaella Palazzo, Barbara Marinari, Immacolata Pietraforte, Giancarlo Santiago Santos, Yves Mattenberger, Francesca Spadaro, Katia Stefanantoni, Nicoletta Iannace, Aleksandra Maria Dufour, Mario Falchi, Manuela Bianco, Elisabetta Botti, Luca Bianchi, Montserrat Alvarez, Valeria Riccieri, Marie-Elise Truchetet, Gerard C.L. Wong (), Carlo Chizzolini and Loredana Frasca ()
Additional contact information
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)

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09683-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09683-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09683-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().