{
  "abstract": "Although coronavirus disease 2019 (COVID-19) is associated with gastrointestinal symptoms and systemic hyperinflammation, the epigenetic mechanisms linking SARS-CoV-2 to intestinal immune activation remain poorly understood. We investigated histone modifications in human ileum immune cells following ex vivo exposure to the recombinant SARS-CoV-2 spike protein using mass cytometry. Cytokine expression (TNF-α, IFN-γ, IL-17A, IL-6, and IL-10) and 14 histone marks were evaluated across eight major immune cell subsets, including B cells, T cells, resident T cells, natural killer (NK) cells, NKT cells, γδ T cells, mucosal-associated invariant T (MAIT) cells, and macrophages (MФ). Spike protein exposure induced coordinated inflammatory cytokine responses accompanied by extensive cell-type-specific epigenetic remodeling. MAIT cells, resident T cells, conventional T cells, and MФ exhibited the greatest chromatin remodeling. In contrast, NK cells, NKT cells, B cells, and γδ T cells showed no or few significant epigenetic changes. Linear mixed-effects modeling indicated that epigenetic associations with inflammatory responses were primarily attributable to differences between donors rather than variation among cell subsets within the same donor. Cell-subset identity remained independently associated with inflammatory response, with resident T cells showing significantly higher inflammatory scores, while the other cell subsets did not differ significantly. Together, these findings suggest that interindividual epigenetic variation and cell-subset identity are key determinants of intestinal inflammatory responses to SARS-CoV-2 spike protein.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "H. Chen"
    },
    {
      "name": "J. Bailey"
    },
    {
      "name": "E. Mezghanni"
    },
    {
      "name": "M. B. Sztein"
    },
    {
      "name": "A. C. Bafford"
    },
    {
      "name": "R. Salerno-Goncalves",
      "orcid": "0000-0003-2999-4275"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8w7kmnvfd7vkw.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-72904-1",
  "fulltext_url": "https://doi.org/10.1038/s41598-026-72904-1",
  "id": "8w7kmnvfd7vkw",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://www.nature.com/articles/s41598-026-72904-1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7223112844",
  "pdf_url": "https://www.nature.com/articles/s41598-026-72904-1.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-21",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/8w7kmnvfd7vkw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:33Z",
      "native_id": "10.1038/s41598-026-72904-1",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41598-026-72904-1"
    },
    {
      "first_seen": "2026-10-30T13:45:53Z",
      "native_id": "484f4ecba6bd46bf8cf764d718652767",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41598-026-72904-1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Cell-type and donor-level epigenetic variation shape intestinal inflammatory responses to SARS-CoV-2 spike protein",
  "title_text": "Cell-type and donor-level epigenetic variation shape intestinal inflammatory responses to SARS-CoV-2 spike protein",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:53Z",
  "url": "https://research.draconitic.com/paper/8w7kmnvfd7vkw",
  "venue": "Scientific Reports",
  "versions": []
}