{
  "abstract": "Introduction: Neutrophil extracellular traps (NETs) are important effectors of innate immunity but can contribute to inflammatory pathology when dysregulated. Although reactive oxygen species (ROS) are known to promote NET formation, the metabolic mechanisms that regulate NETosis remain incompletely understood. Here, we investigated whether modulation of intracellular NAD⁺/NADH redox balance regulates NET formation and inflammatory responses.\n\nMethods: Using primary neutrophils, differentiated HL-60 cells, and an imiquimod-induced psoriasis-like mouse model, we investigated the effects of dunnione, an NQO1 substrate, on NET formation and inflammatory responses.\n\nResults: Dunnione significantly suppressed NET formation and inflammation. Dunnione increased the intracellular NAD⁺/NADH ratio in an NQO1-dependent manner and was accompanied by increased SIRT1 activity. This effect was associated with suppression of PAD4-mediated histone H3 citrullination and attenuation of NF-κB-dependent pro-inflammatory cytokine expression via deacetylation. In addition, dunnione reduced ROS generation and NOX2 activation, further limiting NET formation. The inhibitory effect of dunnione on NET formation was lost under NQO1-deficient conditions, indicating that NQO1 is required for dunnione responsiveness rather than for NET formation itself. In vivo , dunnione significantly attenuated psoriasis-like skin inflammation in association with reduced NET formation and inflammatory responses.\n\nDiscussion: Collectively, these findings support a metabolic mechanism in which NQO1-dependent redox modulation, accompanied by NAD ⁺ SIRT1-associated signaling, contributes to the suppression of NETosis and inflammatory responses.",
  "abstract_shown": true,
  "affiliations": [
    "Biomedical Science, Wonkwang University School of Medicine",
    "Center for Metabolic Function Regulation (CMFR) and Department of Microbiology, Wonkwang University School of Medicine",
    "NADIANBIO Ltd, Wonkwang University School of Medicine",
    "Department of Biochemistry & Molecular Biology, Institute of Medical Science, Jeonbuk National University Medical School",
    "Department of Biochemistry, Wonkwang University School of Medicine",
    "Sarcopenia Total Solution Center, Wonkwang University School of Medicine",
    "Institute of Wonkwang Medical Science, Wonkwang University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Meng-Yu Zhu"
    },
    {
      "affs": [
        2
      ],
      "name": "Seung-Hoon Lee"
    },
    {
      "affs": [
        2
      ],
      "name": "Gi-Su Oh"
    },
    {
      "affs": [
        3
      ],
      "name": "Jong-Suk Kim"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Jae Ho Seo"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Hong-Seob So"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/czndc1ns1qjeb.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1973758",
  "fulltext_url": null,
  "id": "czndc1ns1qjeb",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973758/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Neutrophil, Myeloperoxidase and Oxidative Mechanisms"
    ]
  ],
  "openalex": "W7223184036",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1973758/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/czndc1ns1qjeb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1973758",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973758/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Neutrophil, Myeloperoxidase and Oxidative Mechanisms",
      "subfield": "immunology"
    }
  ],
  "title": "Metabolic control of NETosis: dunnione suppresses inflammatory responses through NQO1–dependent redox modulation",
  "title_text": "Metabolic control of NETosis: dunnione suppresses inflammatory responses through NQO1–dependent redox modulation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/czndc1ns1qjeb",
  "venue": "Frontiers in Immunology",
  "versions": []
}