{
  "abstract": "CD8⁺ T cells, as the most important cytolytic cells in adaptive immunity, can differentiate into distinct subpopulations with specific functions and fates. During this process, CD8⁺ T cells exhibit substantial plasticity in their differentiation trajectory. Notably, epigenetic regulation has emerged as a pivotal mechanism to govern T cell fate decisions. In this study, we demonstrate that the histone methyltransferase NSD2 critically regulates CD8⁺ T cell differentiation during acute viral infection. While NSD2 deficiency enhances the early expansion of activated CD8⁺ T cells, it severely compromises their survival fitness during the contraction phase, leading to a disproportionate collapse of the antigen-specific pool and limiting the establishment of robust long-lived memory. Mechanistically, this defect is driven by the disruption of the H3K36me2-Zbtb20 regulatory axis. Furthermore, we show that in the absence of NSD2, CD8⁺ T cells in tumor exhibit an increased proportion but dysfunctional resident memory T cell phenotype. Collectively, our findings highlight a critical role for NSD2 in providing more mechanistic insights into how epigenetic mechanisms fine-tune T cell differentiation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.",
    "Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.",
    "Department of Otolaryngology–Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.",
    "Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
    "Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.",
    "State Key Laboratory of Oncology in South China, Department of Experiment Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.",
    "Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden.",
    "The Second Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, Guangzhou 510260, China.",
    "Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.",
    "State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan 430030, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shijie Yuan",
      "orcid": "0009-0003-7620-7809"
    },
    {
      "affs": [
        1
      ],
      "name": "Yifan Xu",
      "orcid": "0009-0000-3243-8195"
    },
    {
      "affs": [
        2
      ],
      "name": "Huicheng Liu"
    },
    {
      "affs": [
        3
      ],
      "name": "Ying Xue"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengdi Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaorong Xie"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuwei Wu",
      "orcid": "0009-0008-2824-8151"
    },
    {
      "affs": [
        4
      ],
      "name": "Yuting Xia",
      "orcid": "0000-0002-8530-7380"
    },
    {
      "affs": [
        5
      ],
      "name": "Lin Li"
    },
    {
      "affs": [
        6
      ],
      "name": "Yuan Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Zehan Huang"
    },
    {
      "affs": [
        7
      ],
      "name": "Xiangping Yang"
    },
    {
      "affs": [
        8
      ],
      "name": "Huiyun Du",
      "orcid": "0009-0006-8641-9997"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "Ran He",
      "orcid": "0000-0001-5046-1321"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5pcvn8azabcs6.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aee9670",
  "fulltext_url": "https://europepmc.org/articles/PMC13693679",
  "id": "5pcvn8azabcs6",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aee9670",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "2403|T-cell and B-cell Immunology"
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  "pdf_url": "https://europepmc.org/articles/PMC13693679?pdf=render",
  "pmcid": "PMC13693679",
  "pmid": "42912999",
  "published": "2026-10-23",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/5pcvn8azabcs6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aee9670",
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      "url": "https://www.science.org/doi/10.1126/sciadv.aee9670"
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    {
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      "native_id": "MED:42912999",
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      "url": "https://europepmc.org/article/MED/42912999"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Histone methyltransferase NSD2 shapes CD8 ⁺ T cell fates through the H3K36me2- Zbtb20 axis",
  "title_text": "Histone methyltransferase NSD2 shapes CD8 ⁺ T cell fates through the H3K36me2- Zbtb20 axis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:03Z",
  "url": "https://research.draconitic.com/paper/5pcvn8azabcs6",
  "venue": "Science Advances",
  "versions": []
}