{
  "abstract": "T lymphocytes are primarily generated in the thymus through a complex process of positive and negative selections. The molecular mechanisms underlying this process are not fully understood. Here, we report that TNFAIP8 (TNF-α-induced protein 8-like) family of polarity proteins mediates T cell development by propagating phosphoinositide signaling in the thymus. Genetic deletion of hematopoietic members of the TNFAIP8 family resulted in dramatic reductions in thymus size, cellularity, and corticomedullary differentiation. Total thymocyte counts in Tnfaip8-deficient mice were reduced by more than 50%, which was associated with marked reductions in T cell numbers in blood and in secondary lymphoid organs, as compared to wild-type mice. Bone marrow chimeric experiments revealed that the thymic developmental defect was hematopoietic cell-intrinsic. TNFAIP8 proteins controlled double negative (DN) thymocyte proliferation and metabolism during positive selection by promoting PI3K-AKT/mTOR signaling through phosphoinositide second messengers. Pharmaceutical activation of AKT partially rectified the thymic developmental defect of Tnfaip8-deficient mice. Thus, TNFAIP8 polarity proteins are essential for thymic development of T lymphocytes, and genetic or pharmaceutical manipulation of the TNFAIP8 pathway may be useful for controlling T lymphocyte-mediated immunity.",
  "abstract_shown": true,
  "affiliations": [
    "Henan Health Commission Key Laboratory of Gastrointestinal Cancer Prevention and Treatment, Department of Gastroenterology, The First Affiliated Hospital of Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China.",
    "Henan International Joint Laboratory of Immunology and Model Animals, School of Medical Technology, Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China.",
    "Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Medical Technology, Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China.",
    "School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China.",
    "Center of Translational Medicine, Zibo Central Hospital, Shandong University, Zibo, China.",
    "School of Basic Medical Sciences, Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China.",
    "Department of Radiation Oncology, The First Affiliated Hospital of Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China.",
    "Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen, China. yh.chen@siat.ac.cn.",
    "Henan Health Commission Key Laboratory of Gastrointestinal Cancer Prevention and Treatment, Department of Gastroenterology, The First Affiliated Hospital of Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China. ctminmail@163.com.",
    "Henan International Joint Laboratory of Immunology and Model Animals, School of Medical Technology, Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China. wanghui@xxmu.edu.cn.",
    "Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Medical Technology, Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China. wanghui@xxmu.edu.cn.",
    "School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China. wanghui@xxmu.edu.cn.",
    "Henan Health Commission Key Laboratory of Gastrointestinal Cancer Prevention and Treatment, Department of Gastroenterology, The First Affiliated Hospital of Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China. ylou@xxmu.edu.cn.",
    "Henan International Joint Laboratory of Immunology and Model Animals, School of Medical Technology, Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China. ylou@xxmu.edu.cn.",
    "Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Medical Technology, Henan Medical University (original name: Xinxiang Medical University), Xinxiang, China. ylou@xxmu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jingtao Gao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Cun Guo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yang Lv"
    },
    {
      "affs": [
        1
      ],
      "name": "Han Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Sheng Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Peili Zhuang"
    },
    {
      "affs": [
        1
      ],
      "name": "Miaomiao Song"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Xueqin Tian"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Shan Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Wei Lu"
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    {
      "affs": [
        1,
        2
      ],
      "name": "Lu Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Peiqing Zhao",
      "orcid": "0000-0002-9311-1927"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaohan Wu"
    },
    {
      "affs": [
        5
      ],
      "name": "Xiangfeng Song"
    },
    {
      "affs": [
        6
      ],
      "name": "Xiaohong Kang"
    },
    {
      "affs": [
        7
      ],
      "name": "Youhai H Chen",
      "orcid": "0000-0002-9695-6757"
    },
    {
      "affs": [
        8
      ],
      "name": "Tingmin Chang"
    },
    {
      "affs": [
        9,
        10,
        11
      ],
      "name": "Hui Wang",
      "orcid": "0000-0002-2454-3814"
    },
    {
      "affs": [
        12,
        13,
        14
      ],
      "name": "Yunwei Lou",
      "orcid": "0000-0001-8296-0395"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/efen1cz0tp71h.bib",
  "cited_by": 0,
  "doi": "10.1038/s41419-026-09100-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13686962",
  "id": "efen1cz0tp71h",
  "issns": [
    "2041-4889"
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  "landing_url": "https://europepmc.org/article/MED/42907424",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "lcc",
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      "2403|T-cell and B-cell Immunology"
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  "pdf_url": "https://europepmc.org/articles/PMC13686962?pdf=render",
  "pmcid": "PMC13686962",
  "pmid": "42907424",
  "published": "2026-07-01",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/efen1cz0tp71h.ris",
  "sources": [
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      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42907424",
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
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  ],
  "title": "TNFAIP8 polarity proteins mediate T cell development by propagating lipid second messenger signaling in thymocytes.",
  "title_text": "TNFAIP8 polarity proteins mediate T cell development by propagating lipid second messenger signaling in thymocytes.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:20:51Z",
  "url": "https://research.draconitic.com/paper/efen1cz0tp71h",
  "venue": "Cell death & disease",
  "versions": []
}