Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Nina Kessler - , Universitätsklinikum Bonn (Autor:in)
  • Susanne F Viehmann - , Universitätsklinikum Bonn (Autor:in)
  • Calvin Krollmann - , Universitätsklinikum Bonn (Autor:in)
  • Karola Mai - , Universitätsklinikum Bonn (Autor:in)
  • Katharina M Kirschner - , Universitätsklinikum Bonn (Autor:in)
  • Hella Luksch - , Klinik und Poliklinik für Kinder- und Jugendmedizin, Technische Universität Dresden (Autor:in)
  • Prasanti Kotagiri - , University of Cambridge (Autor:in)
  • Alexander M C Böhner - , Universitätsklinikum Bonn (Autor:in)
  • Dennis Huugen - , Maastricht University (Autor:in)
  • Carina C de Oliveira Mann - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Simon Otten - , Universitätsklinikum Aachen (Autor:in)
  • Stefanie A I Weiss - , Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt, Klinikum der Ludwig-Maximilians-Universität (LMU) München (Autor:in)
  • Thomas Zillinger - , Universitätsklinikum Bonn (Autor:in)
  • Kristiyana Dobrikova - , Universitätsklinikum Bonn (Autor:in)
  • Dieter E Jenne - , Klinikum der Ludwig-Maximilians-Universität (LMU) München, Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (Autor:in)
  • Rayk Behrendt - , Universitätsklinikum Bonn (Autor:in)
  • Andrea Ablasser - , Amsterdam Institute for Global Health and Development (Autor:in)
  • Eva Bartok - , Universitätsklinikum Bonn (Autor:in)
  • Gunther Hartmann - , Universitätsklinikum Bonn (Autor:in)
  • Karl-Peter Hopfner - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Paul A Lyons - , University of Cambridge (Autor:in)
  • Peter Boor - , Universitätsklinikum Aachen (Autor:in)
  • Angela Rösen-Wolff - , Klinik und Poliklinik für Kinder- und Jugendmedizin, Technische Universität Dresden (Autor:in)
  • Lino L Teichmann - , Universitätsklinikum Bonn (Autor:in)
  • Peter Heeringa - , University of Groningen (Autor:in)
  • Christian Kurts - , Universitätsklinikum Bonn (Autor:in)
  • Natalio Garbi - , Universitätsklinikum Bonn (Autor:in)


Autoimmune vasculitis is a group of life-threatening diseases, whose underlying pathogenic mechanisms are incompletely understood, hampering development of targeted therapies. Here, we demonstrate that patients suffering from anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) showed increased levels of cGAMP and enhanced IFN-I signature. To identify disease mechanisms and potential therapeutic targets, we developed a mouse model for pulmonary AAV that mimics severe disease in patients. Immunogenic DNA accumulated during disease onset, triggering cGAS/STING/IRF3-dependent IFN-I release that promoted endothelial damage, pulmonary hemorrhages, and lung dysfunction. Macrophage subsets played dichotomic roles in disease. While recruited monocyte-derived macrophages were major disease drivers by producing most IFN-β, resident alveolar macrophages contributed to tissue homeostasis by clearing red blood cells and limiting infiltration of IFN-β-producing macrophages. Moreover, pharmacological inhibition of STING, IFNAR-I, or its downstream JAK/STAT signaling reduced disease severity and accelerated recovery. Our study unveils the importance of STING/IFN-I axis in promoting pulmonary AAV progression and identifies cellular and molecular targets to ameliorate disease outcomes.


FachzeitschriftThe Journal of experimental medicine
PublikationsstatusVeröffentlicht - 3 Okt. 2022

Externe IDs

PubMedCentral PMC9402992
Scopus 85137123988
WOS 000862391200001



  • Animals, Interferon Type I, Lung, Macrophages, Membrane Proteins/metabolism, Mice, Nucleic Acids, Nucleotidyltransferases, Vasculitis, Sting activation, Glomerulonephritis, Dendritic cells, Neutrophils, I interferon, Cgas, Myeloperoxidase, Mitochondrial-dna, Cyclic gmp-amp, Cytosolic dna