{
  "abstract": "Systemic lupus erythematosus (SLE) links persistent immune dysregulation to heterogeneous tissue injury, but the mechanisms that localise damage remain incompletely resolved. Pyroptosis is a gasdermin-mediated, pore-forming process that can connect nucleic-acid sensing and inflammasome activation to mediator release and tissue-cell dysfunction. Here, we evaluate the SLE and lupus nephritis (LN) literature along two independent axes: mechanistic evidence for pathway licensing, inflammasome activation, gasdermin execution, or terminal lysis, and disease relevance across non-lupus models, lupus models, patient-derived cells, human renal tissue, and longitudinal cohorts. Four conclusions emerge. First, execution-level evidence is confined to a few nodes, including oxidised mitochondrial DNA-driven GSDMD oligomerisation, myeloid caspase-11/GSDMD signalling, and GSDME-mediated tubular epithelial injury; most reported lupus “pyroptosis axes” demonstrate licensing or inflammasome activation only. Second, the direction of GSDMD function remains unresolved: pharmacological inhibition ameliorates experimental lupus, whereas genetic deficiency worsens autoimmunity, renal and pulmonary inflammation, and myeloid calcium homeostasis. Third, the tubulointerstitial compartment carries the strongest executor-level causal evidence in the kidney, whereas glomerular studies offer broader regulatory hypotheses but weaker execution-level proof. Fourth, no current biomarker is execution-specific, and no intervention has demonstrated executor target engagement in patients. We therefore present immune-tissue crosstalk as an evidence-graded framework rather than a demonstrated end-to-end circuit and define the spatial, longitudinal, and lineage-specific studies needed for mechanism-guided translation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Review",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Jia Fan"
    },
    {
      "name": "Kaili Zheng"
    },
    {
      "name": "Li Hua"
    },
    {
      "name": "Xuelian Hong"
    },
    {
      "name": "Hongwei Du"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e2qrp6mffaqd3.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1976486",
  "fulltext_url": null,
  "id": "e2qrp6mffaqd3",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976486",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e2qrp6mffaqd3.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T18:20:17Z",
      "native_id": "10.3389/fimmu.2026.1976486",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976486"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Pyroptosis in systemic lupus erythematosus and lupus nephritis: evidence grading, cellular crosstalk, and translational priorities",
  "title_text": "Pyroptosis in systemic lupus erythematosus and lupus nephritis: evidence grading, cellular crosstalk, and translational priorities",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T18:20:17Z",
  "url": "https://research.draconitic.com/paper/e2qrp6mffaqd3",
  "venue": "Frontiers in Immunology",
  "versions": []
}