{
  "abstract": "Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by systemic immune activation and multi-organ inflammation. Granzyme K (GZMK), a serine protease predominantly expressed by CD8+ T cells and natural killer cells, has emerging non-cytotoxic inflammatory functions, but its relevance to SLE remains incompletely defined. In this study, we conducted investigations using plasma and tissue analyses, single-cell RNA sequencing, proteomics, multiplex immunofluorescence, an animal model, and primary human B cell experiments. Plasma GZMK was increased in patients with SLE and was associated with clinical disease activity. Integrated multi-tissue single cell analysis identified preferential GZMK enrichment in CD8+ effector memory T (Tem) cells and a higher relative abundance of this compartment in SLE, while proteomic profiling and multiplex immunofluorescence provided protein and tissue level evidence for a GZMK-enriched CD8+ memory T cell population. Cell–cell communication analysis suggested enhanced predicted communication between Tem and B lineage cells, and circulating GZMK was further associated with a plasma cell-like population. In two murine models, PPACK, which can inhibit GZMK catalytic activity but is not GZMK selective, attenuated lupus associated inflammatory phenotypes and partially normalized altered splenic B cell composition. In vitro experiments showed that active recombinant GZMK augmented plasma-cell-associated phenotypic and transcriptional responses under B cell expansion conditions. Collectively, these findings identify circulating GZMK as an independent correlate of SLE clinical activity and characterize a recurrent GZMK-enriched CD8+ memory/Tem cell program across peripheral blood and affected tissues that is associated with B-cell dysregulation and plasma-cell-related immune abnormalities.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Yunjing Pu"
    },
    {
      "name": "Zhongyu Chen"
    },
    {
      "name": "Peihui Yang"
    },
    {
      "name": "Qinghuan Zhu"
    },
    {
      "name": "Haojun Long"
    },
    {
      "name": "Yali Zhou"
    },
    {
      "name": "Danqi Deng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3fdbkdmchataf.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1934348",
  "fulltext_url": null,
  "id": "3fdbkdmchataf",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1934348",
  "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": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/3fdbkdmchataf.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T06:20:39Z",
      "native_id": "10.3389/fimmu.2026.1934348",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1934348"
    },
    {
      "first_seen": "2026-11-04T12:21:26Z",
      "native_id": "10.3389/fimmu.2026.1934348",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1934348/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Granzyme K associates with inflammatory immune programs and B-cell dysregulation in systemic lupus erythematosus",
  "title_text": "Granzyme K associates with inflammatory immune programs and B-cell dysregulation in systemic lupus erythematosus",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:26Z",
  "url": "https://research.draconitic.com/paper/3fdbkdmchataf",
  "venue": "Frontiers in Immunology",
  "versions": []
}