{
  "abstract": "T cells in patients with chronic autoimmunity show features of dysfunction. However, the functionally defined T cell subsets that are affected by these changes remain poorly characterized. Here, we sought to reveal aberrations in the composition, phenotype, and function of canonical T cell subsets in the blood of systemic sclerosis (SSc) patients compared with healthy subjects and systemic lupus erythematosus (SLE) patients. Therefore, we developed a novel multidimensional flow-cytometry panel to simultaneously detect lineage-defining transcription factors, co-inhibitory receptors and other functional markers to characterize T cell subsets without in vitro restimulation. We compared T cell landscapes in SSc and SLE patients, and healthy subjects, using opt-SNE (optimized t-distributed stochastic neighbor embedding) and PhenoGraph algorithms. The data show altered distribution and aberrant functional states of transcription factor–defined T cell subsets in patients with autoimmunity, with shared and unique features between diseases and their subtypes. Strikingly, SSc and SLE patients showed deficiencies in subsets of CD8+ and CD4−CD8− T cells that expressed T-bet, which is critical for IFN-γ–dependent type 1 immunity. Moreover, TIGIT+Foxp3+ regulatory T cells, which suppress T helper 1 responses, were increased in diffuse cutaneous SSc and SLE patients. Functionally, T cells from SSc patients produced less IFN-γ, a cytokine that suppresses profibrotic gene expression in fibroblasts, as we demonstrate by transcriptomic analysis. Our study supports a model in which IFN-γ opposes canonical fibrotic gene programs in fibroblasts, and deficiencies in the IFN-γ–producing T cell compartment in SSc patients therefore may contribute to chronic fibrosis development. Aberrant T cell subsets in SSc and SLE represent targets for corrective immunotherapy.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Victoria Volfson-Sedletsky"
    },
    {
      "name": "Hannah A DeBerg",
      "orcid": "0000-0002-5263-158X"
    },
    {
      "name": "Mitch L Fahning",
      "orcid": "0000-0001-9352-4409"
    },
    {
      "name": "Ian R Rifkin",
      "orcid": "0000-0002-2674-3991"
    },
    {
      "name": "Andreea M Bujor",
      "orcid": "0000-0002-8840-8937"
    },
    {
      "name": "Daniel J Campbell",
      "orcid": "0000-0002-9652-7178"
    },
    {
      "name": "Peter A Morawski",
      "orcid": "0000-0001-9159-4032"
    },
    {
      "name": "Anna C Belkina",
      "orcid": "0000-0001-7967-6254"
    },
    {
      "name": "Hans Dooms",
      "orcid": "0000-0001-7964-0876"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/394rt25redne7.bib",
  "cited_by": 0,
  "doi": "10.1093/jimmun/vkag288",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735513/",
  "id": "394rt25redne7",
  "issns": [
    "0022-1767",
    "1550-6606"
  ],
  "landing_url": "https://doi.org/10.1093/jimmun/vkag288",
  "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",
      "AcademicSubjects/MED00010"
    ],
    [
      "heading",
      "AcademicSubjects/MED00690"
    ],
    [
      "heading",
      "AcademicSubjects/MED00730"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "Special Issue: Clinical and Human Immunology"
    ],
    [
      "openalex",
      "2745|Systemic Sclerosis and Related Diseases"
    ]
  ],
  "openalex": "W7115073726",
  "pdf_url": "https://academic.oup.com/jimmunol/article-pdf/215/11/vkag288/73040816/vkag288.pdf",
  "pmcid": "PMC13735513",
  "pmid": "42982762",
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/394rt25redne7.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:11Z",
      "native_id": "PMC13735513",
      "source": "pmc",
      "url": "https://doi.org/10.1093/jimmun/vkag288"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "journal-openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "The altered T cell landscape in systemic sclerosis patients is characterized by dysfunctional type 1 immunity",
  "title_text": "The altered T cell landscape in systemic sclerosis patients is characterized by dysfunctional type 1 immunity",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:11Z",
  "url": "https://research.draconitic.com/paper/394rt25redne7",
  "venue": "The Journal of Immunology Author Choice",
  "versions": []
}