{
  "abstract": "Crohn's disease (CD)-associated mucosal injury involves immune-cell infiltration, epithelial cell death, and junctional disruption, but how specific myeloid states contribute to epithelial lipid peroxidation remains unclear. We integrated longitudinal single-cell transcriptomics, spatial transcriptomics, macrophage–epithelial co-culture, epithelial RNA-seq, exploratory candidate-gene prioritization, GPX4 functional validation, and a TNBS-induced chronic colitis model to investigate IL1B-high macrophage-associated epithelial injury. In paired pretreatment and post-treatment biopsies, persistent active disease (POST-ACT) showed a higher relative representation of myeloid cells, increased epithelial programmed-cell-death-related transcriptional activity, and stronger predicted myeloid–epithelial communication than remission samples. Myeloid subclustering identified a pro-inflammatory IL1B-high macrophage state relatively enriched in pooled POST-ACT cells, while RCTD-based spatial mapping supported non-random local co-occurrence of inferred IL1B-high macrophage and injury-associated epithelial signals. In vitro, IL1B-high macrophage co-culture increased epithelial cell death, reduced GSH, and increased MDA and lipid ROS in FHC and NCM460 cells; these changes were partially attenuated by Ferrostatin-1. Integration of ferroptosis-related genes, differential expression, LASSO, and random forest prioritized GPX4, PGD, and LPCAT3. GPX4 was consistently downregulated and was selected for functional validation; GPX4 overexpression partially restored ZO-1, E-cadherin, and Occludin expression. Blocking IL-1β/IL1R1 signaling with an anti-IL-1β neutralizing antibody or the IL1R1 antagonist AF12198 attenuated lipid peroxidation, GPX4 downregulation, and loss of junction-associated molecules in the shared co-culture system. In TNBS colitis, Ferrostatin-1 or anti-IL-1β treatment alleviated selected mucosal injury phenotypes, and adding IL-1β blockade to anti-TNF produced incremental improvement over anti-TNF alone. Collectively, these findings support an IL1B-high macrophage-associated epithelial injury axis involving IL-1β–IL1R1 signaling, reduced GPX4-related lipid-peroxide defense, ferroptosis-like lipid peroxidation injury, and junction-associated molecular alterations in CD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China",
    "Department of Anorectal Surgery, The First People's Hospital of Chenzhou, Chenzhou, Hunan, 423000, China",
    "Fourth Department of Internal Medicine, Chenggong District People's Hospital of Kunming, Kunming, Yunnan, 650500, China",
    "Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China; Corresponding author. Department of General Surgery, The Second Xiangya Hospital of Central South University, 410011 Changsha, China."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qi Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhixian Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xueliang Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ganglei Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Mengyao Song"
    },
    {
      "affs": [
        3
      ],
      "name": "Lianwen Yuan"
    },
    {
      "affs": [
        3
      ],
      "name": "Lichao Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8sckkm3sg7rsp.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104403",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2213231726004027",
  "id": "8sckkm3sg7rsp",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://doi.org/10.1016/j.redox.2026.104403",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "lcc",
      "R5-920"
    ],
    [
      "openalex",
      "1311|Inflammatory Bowel Disease"
    ]
  ],
  "openalex": "W7212951577",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/8sckkm3sg7rsp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:15Z",
      "native_id": "5a545df4ff334ac292efa176552fb317",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.redox.2026.104403"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Inflammatory Bowel Disease",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "IL1B-high macrophages promote ferroptosis-like lipid peroxidation injury in Crohn's disease intestinal epithelium",
  "title_text": "IL1B-high macrophages promote ferroptosis-like lipid peroxidation injury in Crohn's disease intestinal epithelium",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:15Z",
  "url": "https://research.draconitic.com/paper/8sckkm3sg7rsp",
  "venue": "Redox Biology",
  "versions": []
}