{
  "abstract": "The tyrosine kinase ZAP-70 is essential for T-cell activation and development, but the mechanisms regulating its activity remain unclear. Previous studies showed that the Src-family kinase LCK binds phosphorylated tyrosine 319 of ZAP-70 via its SH2 domain. Additionally, a gain-of-function ZAP-70 mutation involving the YEEI motif enhances LCK recruitment and TCR-mediated signaling. To investigate the physiological consequences of enhanced ZAP-70-LCK interaction in vivo , we generated a knock-in mouse model expressing the Zap70 YEEI gain-of-function mutation. Analysis of thymocyte development revealed that the Zap70 YEEI mutation altered T-cell maturation, resulting in increased differentiation of thymic regulatory T (Treg) cells and reduced thymic negative selection. In the peripheral T-cell compartment, mutant mice exhibited decreased surface expression of the TCRαβ complex and an increased frequency of memory CD4 T cells. These findings indicate that enhancing the ZAP-70-LCK interaction modifies signaling thresholds during thymic selection and peripheral T-cell homeostasis. Collectively, our results demonstrate that a gain-of-function mutation in Zap70 significantly reshapes T-cell development and maturation, highlighting the importance of regulated ZAP-70-LCK interactions in establishing immune tolerance and maintaining T-cell compartment balance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedicine, Biotechnology and Public Health, Universidad de Cádiz",
    "Centre d’Immunophénomique (CIPHE), Aix Marseille Université, INSERM, CNRS",
    "Centre d’Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, INSERM, CNRS",
    "School of Medical Technology, Xinxiang Medical University",
    "Institute of Biomedical Research Cadiz (INIBICA)",
    "Laboratory of Immunophenomics, School of Medical Technology, Xinxiang Medical University"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Inmaculada Vico-Barranco"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Fanghui Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Claude Grégoire"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Luis M. Fernández-Aguilar"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Mikel M. Arbulo-Echevarria"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Isaac Narbona-Sánchez"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Raquel Muñoz-Fernández"
    },
    {
      "affs": [
        1,
        2,
        3,
        5
      ],
      "name": "Bernard Malissen"
    },
    {
      "affs": [
        1,
        2,
        3,
        5
      ],
      "name": "Marie Malissen"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Enrique Aguado"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e9g3wn2gffbs7.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1932213",
  "fulltext_url": "https://europepmc.org/articles/PMC13680439",
  "id": "e9g3wn2gffbs7",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1932213/full",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7220684227",
  "pdf_url": "https://europepmc.org/articles/PMC13680439?pdf=render",
  "pmcid": "PMC13680439",
  "pmid": "42903192",
  "published": "2026-10-06",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/e9g3wn2gffbs7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1932213",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1932213/full"
    },
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42903192",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42903192"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "A Zap70 gain-of-function mutation alters mouse thymic maturation",
  "title_text": "A Zap70 gain-of-function mutation alters mouse thymic maturation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/e9g3wn2gffbs7",
  "venue": "Frontiers in Immunology",
  "versions": []
}