{
  "abstract": "IntroductionAcute graft-versus-host disease (aGVHD) of the gastrointestinal tract remains a leading cause of non-relapse mortality following allogeneic hematopoietic cell transplantation, and steroid-refractory intestinal aGVHD carries a particularly poor prognosis. CD8+ T cells are critical effectors of intestinal tissue injury, yet the molecular mechanisms underlying their pathogenic role remain incompletely understood, especially in the steroid-refractory state.MethodsThis study aimed to identify key biomarker genes associated with CD8+ T cell-mediated intestinal aGVHD and to characterize their expression dynamics in the steroid-refractory state. Integrative bioinformatics analysis was performed using the Gene Expression Omnibus dataset GSE79083 (a CD8+ T cell-dependent murine aGVHD model), with a human dataset (GSE134662) for independent validation. Hub genes were prioritized through protein–protein interaction network analysis and random forest machine learning. A murine aGVHD model was established for validation via clinical score, qRT-PCR, histopathology, and immunofluorescence double staining.ResultsLag3 was identified as the top-ranked gene with high diagnostic discrimination. In the murine model, Lag3 was markedly upregulated in intestinal tissue of the aGVHD group, and immunofluorescence confirmed CD8+ LAG3+ T cell infiltration of the intestinal mucosa. Notably, the steroid-refractory group exhibited more severe colonic histopathological injury. In this group, Lag3 expression was significantly lower than in the aGVHD group despite persistent CD8+ T cell infiltration. A similar expression pattern was observed in the human dataset.ConclusionThe reduction of Lag3 despite persistent severe tissue injury suggests that glucocorticoid-resistant CD8+ T cells may have escaped checkpoint-mediated restraint. These findings suggest a dual-pathology framework for steroid-refractory intestinal aGVHD, involving both effector mechanisms independent of LAG3 and impaired epithelial repair. Whether targeting both processes in combination would be beneficial remains to be tested.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "Qiaoqiao Xia"
    },
    {
      "name": "Yuting Liu"
    },
    {
      "name": "Wenying Ning"
    },
    {
      "name": "Yunyan He"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9c2f75fqsdp6w.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1973310",
  "fulltext_url": null,
  "id": "9c2f75fqsdp6w",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973310",
  "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": "2026-11-03",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/9c2f75fqsdp6w.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T06:20:16Z",
      "native_id": "10.3389/fimmu.2026.1973310",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973310"
    },
    {
      "first_seen": "2026-11-03T12:21:20Z",
      "native_id": "10.3389/fimmu.2026.1973310",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973310/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Differential LAG3 expression in intestinal tissue reveals a dual-pathology model of steroid-refractory acute graft-versus-host disease",
  "title_text": "Differential LAG3 expression in intestinal tissue reveals a dual-pathology model of steroid-refractory acute graft-versus-host disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T00:21:02Z",
  "url": "https://research.draconitic.com/paper/9c2f75fqsdp6w",
  "venue": "Frontiers in Immunology",
  "versions": []
}