{
  "abstract": "Background: Acute allograft rejection is largely dependent on T cell‐driven immune responses; however, the molecular programs that establish and maintain effector T cell states during rejection remain incompletely defined.\n\nMethods: Single‐cell transcriptomic analysis was conducted to characterize the activation of signalling pathways in T cells during acute allograft rejection. The function of MEK1/2 signalling was evaluated both in vitro and in vivo using mice with targeted deletion of Mek1/2 in T cells and pharmacological inhibition. Phosphoproteomic analysis, immunofluorescence staining, and western blotting were conducted to investigate downstream signalling mechanisms, particularly those involving SMAD4.\n\nResults: Effector CD4 and CD8 T cells exhibited enhanced MEK/ERK pathway activation throughout the rejection process. MEK1/2 inhibition, either via genetic deletion or pharmacological blockade, attenuated T cell activation and effector activity, leading to reduced rejection and prolonged graft survival. Phosphoproteomic analysis identified SMAD4 as a key downstream effector of MEK1/2 signalling. Mechanistically, MEK1/2 deficiency reduced SMAD4 nuclear translocation in activated T cells, accompanied by diminished effector T cell responses.\n\nConclusions: MEK1/2 signalling regulates T cell activation and effector phenotypes via SMAD4 nuclear translocation in heart transplant rejection. Therapeutic intervention targeting this pathway may contribute to alloimmune response regulation and improve transplant outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China",
    "Center for Translational Medicine, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China",
    "Institute of Translational Medicine, Tongji Medical College Huazhong University of Science and Technology Wuhan China",
    "Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China",
    "Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation Key Laboratory of Organ Transplantation Chinese Academy of Medical Sciences Wuhan China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jiulu Zhao"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Shuan Ran"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Sijie Zhou"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yuan Li"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Wang Zhan"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Longyong Lai"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Jikai Cui",
      "orcid": "0000-0002-8624-8087"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Jiahong Xia",
      "orcid": "0000-0003-2144-7525"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Jie Wu",
      "orcid": "0000-0002-8880-2520"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7t90fxvpmx08m.bib",
  "cited_by": 0,
  "doi": "10.1002/ctm2.70865",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13714352/",
  "id": "7t90fxvpmx08m",
  "issns": [
    "2001-1326"
  ],
  "landing_url": "https://doi.org/10.1002/ctm2.70865",
  "language": "en",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2746|Transplantation: Methods and Outcomes"
    ]
  ],
  "openalex": "W7224083592",
  "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.70865",
  "pmcid": "PMC13714352",
  "pmid": "42947332",
  "published": "2026-10-27",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/7t90fxvpmx08m.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:21:52Z",
      "native_id": "PMC13714352",
      "source": "pmc",
      "url": "https://doi.org/10.1002/ctm2.70865"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Transplantation: Methods and Outcomes",
      "subfield": "surgery"
    }
  ],
  "title": "MEK1/2 Signalling establishes an alloreactive effector T cell program through SMAD4 during cardiac allograft rejection",
  "title_text": "MEK1/2 Signalling establishes an alloreactive effector T cell program through SMAD4 during cardiac allograft rejection",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:52Z",
  "url": "https://research.draconitic.com/paper/7t90fxvpmx08m",
  "venue": "Clinical and Translational Medicine",
  "versions": []
}