{
  "abstract": "Background\n\nNeutrophil extracellular traps (NETs) are implicated in type I interferon (IFN) production in Systemic Lupus Erythematosus (SLE). While NETs are known to activate plasmacytoid dendritic cells (pDCs) via binding to Toll-like receptors, their effects on other immune cells remain underexplored. This study investigated whether NETs in plasma from patients with active SLE trigger cGAS-STING signalling in monocytes and induce the production of type I IFN and other immunomodulatory cytokines.Methods\n\nMonocytes from healthy donors were cultured with diluted plasma from healthy donors or patients with SLE across varying disease activity, or with in vitro-generated NETs. Activation of the cGAS-STING pathway was assessed by flow cytometric analysis of phosphorylated STING (pSTING) and TBK1 (pTBK1). Cytokine production, including type I IFNs, was quantified using bead-based immunoassays. Only female donor samples meeting the study eligibility criteria were available for inclusion in this cohort.Findings\n\nPlasma MPO-DNA levels correlated with IFNβ levels in patients with SLE (P = 0.002). SLE plasma induced STING and TBK1 phosphorylation, and IFNβ expression in healthy monocytes, with responses increasing according to donor disease activity (P < 0.0005). Experiments with healthy monocytes exposed to in vitro-generated NETs recapitulated these findings, evidenced by increased pSTING and pTBK1 expression and enhanced IFNα and IFNβ secretion (P < 0.05), which were inhibited by cGAS-IN-1.Interpretation\n\nOur findings support a role for NET-associated DNA in activating cGAS-STING signalling and promoting type I IFN production by monocytes in SLE. These findings identify NET-mediated cGAS-STING signalling in monocytes as a pathway that warrants further investigation in the context of type I IFN-driven inflammation in SLE.Funding\n\nNot Applicable.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, the Netherlands.",
    "Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, the Netherlands.",
    "Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, the Netherlands; Department of Internal Medicine, Flevo Hospital, Almere, the Netherlands.",
    "Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, the Netherlands; Department of Pediatrics, University Medical Center Utrecht, Utrecht University, the Netherlands. Electronic address: M.L.Boes@umcutrecht.nl."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xiaolin Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Dagmar Duijzer"
    },
    {
      "affs": [
        0
      ],
      "name": "Tineke Kardol-Hoefnagel"
    },
    {
      "affs": [
        1
      ],
      "name": "Bettina C Geertsema-Hoeve"
    },
    {
      "affs": [
        0
      ],
      "name": "Jeanette H W Leusen"
    },
    {
      "affs": [
        2
      ],
      "name": "Maarten Limper"
    },
    {
      "affs": [
        3
      ],
      "name": "Marianne Boes",
      "orcid": "0000-0003-2590-1692"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/03zey9rgqy4kp.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ebiom.2026.106507",
  "fulltext_url": "https://europepmc.org/articles/PMC13675855",
  "id": "03zey9rgqy4kp",
  "issns": [
    "2352-3964"
  ],
  "landing_url": "https://europepmc.org/article/MED/42843114",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2745|Systemic Lupus Erythematosus Research"
    ]
  ],
  "openalex": "W7220858312",
  "pdf_url": "https://europepmc.org/articles/PMC13675855?pdf=render",
  "pmcid": "PMC13675855",
  "pmid": "42843114",
  "published": "2026-10-07",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/03zey9rgqy4kp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "MED:42843114",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42843114"
    },
    {
      "first_seen": "2026-10-30T12:19:49Z",
      "native_id": "10.1016/j.ebiom.2026.106507",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2352396426003919"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Systemic Lupus Erythematosus Research",
      "subfield": "general"
    }
  ],
  "title": "NET-derived DNA is associated with cGAS-STING and type I IFN responses, as supported by monocyte stimulation cultures using plasma from female patients with SLE.",
  "title_text": "NET-derived DNA is associated with cGAS-STING and type I IFN responses, as supported by monocyte stimulation cultures using plasma from female patients with SLE.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:49Z",
  "url": "https://research.draconitic.com/paper/03zey9rgqy4kp",
  "venue": "EBioMedicine",
  "versions": []
}