{
  "abstract": "BACKGROUND: Cardiac allografts show poorer long-term survival and decreased tolerance compared to renal allografts, but the underlying mechanisms remain unclear. METHODS AND RESULTS: We established heterotopic heart and kidney allotransplantation models in Bama miniature pigs. Single-cell RNA sequencing (scRNA-seq) was performed to analyze normal heart/kidney tissues and allografts. Transcription factor analysis focused on T-cell subsets, with key findings validated using clinical human heart tissues (normal vs. acute rejection) and a mouse heart transplantation model (to test MYC inhibition). T/NK (TNK) subsets in cardiac allografts exhibited higher expression of genes linked to immune system activation, mature B-cell differentiation, and immune memory. The TNFRSF4+ CD4+ T-cell subset was selectively expanded in cardiac allografts (but reduced in renal allografts) during acute rejection, with transcriptional analysis identifying MYC as a master regulator of glycolysis-related genes in this subset. In the mouse heart transplant model, inhibition of MYC (via 10058-F4) reduced the proportion of TNFRSF4+ CD4+ T cells and significantly prolonged cardiac allograft survival. CONCLUSIONS: Our study identified a MYC-driven, glycolysis-dependent expansion of TNFRSF4+ CD4+ T cells as a key mechanism contributing to the heightened rejection susceptibility of cardiac allografts (vs. renal allografts). These findings provide a rationale for developing cardiac-targeted immunosuppressive strategies.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Peiyuan Li"
    },
    {
      "name": "Yuan Chang"
    },
    {
      "name": "Xiaofei Zhu"
    },
    {
      "name": "Xiao Chen"
    },
    {
      "name": "Xiumeng Hua"
    },
    {
      "name": "Yixuan Sheng"
    },
    {
      "name": "Ningning Zhang"
    },
    {
      "name": "Qian Zhao"
    },
    {
      "name": "Kai Xing"
    },
    {
      "name": "Xingchao Du"
    },
    {
      "name": "Mengda Xu"
    },
    {
      "name": "Jiangping Song"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/15rwpkz4kkbdv.bib",
  "cited_by": 0,
  "doi": "10.1253/circj.cj-25-0880",
  "fulltext_url": "https://www.jstage.jst.go.jp/article/circj/90/11/90_CJ-25-0880/_article",
  "id": "15rwpkz4kkbdv",
  "issns": [
    "1347-4820",
    "1346-9843"
  ],
  "landing_url": "https://www.jstage.jst.go.jp/article/circj/90/11/90_CJ-25-0880/_article",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "jstage-journal",
      "medicine/cardiovascular"
    ],
    [
      "openalex",
      "2746|Transplantation: Methods and Outcomes"
    ]
  ],
  "openalex": "W7163512945",
  "pdf_url": "https://www.jstage.jst.go.jp/article/circj/advpub/0/advpub_CJ-25-0880/_pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/15rwpkz4kkbdv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10.1253/circj.cj-25-0880",
      "source": "jstage",
      "url": "https://www.jstage.jst.go.jp/article/circj/90/11/90_CJ-25-0880/_article"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Transplantation: Methods and Outcomes",
      "subfield": "surgery"
    }
  ],
  "title": "MYC-Driven Glycolysis in TNFRSF4+ CD4+ T Cells Underlies Heightened Rejection Susceptibility of Cardiac vs. Renal Allografts",
  "title_text": "MYC-Driven Glycolysis in TNFRSF4+ CD4+ T Cells Underlies Heightened Rejection Susceptibility of Cardiac vs. Renal Allografts",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:24Z",
  "url": "https://research.draconitic.com/paper/15rwpkz4kkbdv",
  "venue": "Circulation Journal",
  "versions": []
}