{
  "abstract": "Objective: We aimed to characterize CD4+ T cell plasticity in human systemic lupus erythematosus (SLE) by leveraging T cell receptor (TCR) repertoire features as markers of prior lineage states, integrating TCR and transcriptomic profiling to delineate plasticity patterns and evaluate their association with clinical disease activity.\n\nMethods: We used TCR repertoire data as molecular signatures alongside a transcriptomic data set. Using a large‐scale ImmuNexUT database of patients with autoimmune disease, including 117 with SLE, we quantified T cell plasticity across 13 fine‐grained T cell types. We analyzed 6,392 samples in total. We defined “cell type” and “disease” signatures and evaluated plasticity by correlations between these signatures and by within‐donor TCR clonotype overlap. Replication was performed in independent bulk and single‐cell cohorts.\n\nResults: We identified two orthogonal signatures of the repertoire and transcriptome, the cell type and disease signatures, allowing us to investigate CD4+ T cell plasticity comprehensively. Among all possible patterns, the strongest signal was observed between effector Treg cells (eTreg cells) and Th1 cells, and this was replicated in an independent cohort. SLE Th1 cells exhibited Treg‐like TCR features and transcriptomic profiles, and eTreg cells showed increased clonotype sharing with Th1 cells compared with healthy controls. The Th1 “Tregness” score positively correlated with SLE disease activity.\n\nConclusion: Our study identifies a Treg‐associated Th1 state in human SLE, consistent with Treg cell to Th1 cell plasticity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Allergy and Rheumatology, Graduate School of Medicine The University of Tokyo Tokyo Japan",
    "Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine The University of Tokyo Tokyo Japan",
    "Laboratory for Human Immunogenetics, Center for Integrative Medical Sciences RIKEN Kanagawa Japan",
    "Division of Rheumatology and Clinical Immunology, Department of Medicine Jichi Medical University Tochigi Japan",
    "Center for Data Sciences Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts",
    "Division of Genetics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts",
    "Division of Rheumatology, Inflammation, and Immunity, Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts",
    "Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge Massachusetts",
    "Department of Biomedical Informatics Harvard Medical School Boston Massachusetts",
    "Department of Microbiology and Immunology Keio University School of Medicine Tokyo Japan",
    "Division of Rheumatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan",
    "Keio University Human Biology‐Microbiome‐Quantum Research Center Tokyo Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Yasuo Nagafuchi"
    },
    {
      "affs": [
        2
      ],
      "name": "Masahiro Nakano"
    },
    {
      "affs": [
        4,
        5,
        6,
        7,
        8
      ],
      "name": "Kaitlyn A. Lagattuta"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mineto Ota"
    },
    {
      "affs": [
        2,
        9
      ],
      "name": "Hiroaki Hatano"
    },
    {
      "affs": [
        2,
        9
      ],
      "name": "Haruka Takahashi"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Takahiro Itamiya"
    },
    {
      "affs": [
        2,
        10
      ],
      "name": "Hajime Inokuchi"
    },
    {
      "affs": [
        4,
        5,
        6,
        7,
        8
      ],
      "name": "Soumya Raychaudhuri"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tomohisa Okamura"
    },
    {
      "affs": [
        0
      ],
      "name": "Keishi Fujio",
      "orcid": "0000-0001-7276-5254"
    },
    {
      "affs": [
        2,
        9,
        11
      ],
      "name": "Kazuyoshi Ishigaki"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6747aapsbt54y.bib",
  "cited_by": 6,
  "doi": "10.1002/art.70218",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712554/",
  "id": "6747aapsbt54y",
  "issns": [
    "2326-5191",
    "2326-5205"
  ],
  "landing_url": "https://doi.org/10.1002/art.70218",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Full Length"
    ],
    [
      "heading",
      "Systemic Lupus Erythematosus"
    ],
    [
      "openalex",
      "2745|Systemic Lupus Erythematosus Research"
    ]
  ],
  "openalex": "W4406104979",
  "pdf_url": null,
  "pmcid": "PMC13712554",
  "pmid": "42101025",
  "published": "2026-06-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6747aapsbt54y.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:06Z",
      "native_id": "PMC13712554",
      "source": "pmc",
      "url": "https://doi.org/10.1002/art.70218"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Systemic Lupus Erythematosus Research",
      "subfield": "general"
    }
  ],
  "title": "T Cell Plasticity in Systemic Lupus Erythematosus Revealed by Large‐Scale T Cell Receptor Repertoire and Transcriptome Studies",
  "title_text": "T Cell Plasticity in Systemic Lupus Erythematosus Revealed by Large‐Scale T Cell Receptor Repertoire and Transcriptome Studies",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:06Z",
  "url": "https://research.draconitic.com/paper/6747aapsbt54y",
  "venue": "Arthritis & Rheumatology (Hoboken, N.j.)",
  "versions": []
}