{
  "abstract": "Immune-mediated damage depletes intestinal stem cells (ISCs) and their homeostatic niche. Whether inflammatory injury induces an alternative niche that promotes regeneration remains unknown. Using single-cell spatial transcriptomics in murine gastrointestinal graft-versus-host disease, we identified cytotoxic CD8⁺ T cells accumulated near intestinal crypts coinciding with ISC, Paneth cell depletion, and epithelial death pathway activation. A distinct Dio2⁺ Il11⁺ fibroblast population emerged in regions of maximal intestinal damage between the epithelial progenitors and stromal cells. These fibroblasts expressed cAMP-response and immune-recruitment programs, suggesting niche reorganization. Thyroid hormone receptor antagonism reduced organoid budding, whereas enhancing thyroid hormone signaling promoted morphogenesis, particularly with IL-11, linking local T3 and IL-11 secretion by these Dio2⁺ Il11⁺ cells to ISC regeneration. Similar niches were observed in DSS-induced colitis model and in biopsies from patients with Crohn’s disease. Our data identify Dio2⁺ Il11⁺ fibroblasts as a stromal-endocrine niche at the site of immune injury that supports ISC regeneration.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Pavan Reddy",
      "orcid": "0000-0001-7264-8429"
    },
    {
      "name": "Takashi Ikeda"
    },
    {
      "name": "Akira Yamamoto",
      "orcid": "0000-0001-7574-6446"
    },
    {
      "name": "Tyler Leach"
    },
    {
      "name": "Kelli McCord"
    },
    {
      "name": "Lihong Xu"
    },
    {
      "name": "Meng-Chih Wu",
      "orcid": "0009-0006-1204-7887"
    },
    {
      "name": "Yuichi Sumii"
    },
    {
      "name": "Neelam Bodhale"
    },
    {
      "name": "Yui Kambara"
    },
    {
      "name": "Victoria Ontiveros",
      "orcid": "0009-0009-9283-7150"
    },
    {
      "name": "Ana Santibanez",
      "orcid": "0000-0002-9231-0975"
    },
    {
      "name": "Dongchang zhao"
    },
    {
      "name": "Yaping Sun"
    },
    {
      "name": "Laure Maneix",
      "orcid": "0000-0003-0044-5395"
    },
    {
      "name": "William Hudson",
      "orcid": "0000-0002-2513-1213"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4xqbc8tf6tyjw.bib",
  "cited_by": 0,
  "doi": "10.21203/rs.3.rs-11143774/v1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13742837/",
  "id": "4xqbc8tf6tyjw",
  "issns": [
    "2693-5015"
  ],
  "landing_url": "https://doi.org/10.21203/rs.3.rs-11143774/v1",
  "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",
      "Article"
    ],
    [
      "openalex",
      "2715|Inflammatory Bowel Disease"
    ]
  ],
  "openalex": "W7222538605",
  "pdf_url": "https://www.researchsquare.com/article/rs-11143774/latest.pdf",
  "pmcid": "PMC13742837",
  "pmid": "42999345",
  "published": "2026-10-16",
  "publisher": "American Journal Experts",
  "ris": "https://research.draconitic.com/paper/4xqbc8tf6tyjw.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:23:36Z",
      "native_id": "PMC13742837",
      "source": "pmc",
      "url": "https://doi.org/10.21203/rs.3.rs-11143774/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2715|Inflammatory Bowel Disease",
      "subfield": "general"
    }
  ],
  "title": "Dio2+Il11+ fibroblasts constitute a local stromal-endocrine niche that promotes intestinal stem cell regeneration after immune-mediated injury",
  "title_text": "Dio2+Il11+ fibroblasts constitute a local stromal-endocrine niche that promotes intestinal stem cell regeneration after immune-mediated injury",
  "type": "preprint",
  "updated_at": "2026-11-10T12:23:36Z",
  "url": "https://research.draconitic.com/paper/4xqbc8tf6tyjw",
  "venue": "Research Square",
  "versions": []
}