{
  "abstract": "Inflammatory bowel disease (IBD) is a chronic condition caused by altered cytokine signaling, maladaptive immunity, dysbiosis, and intestinal barrier dysfunction. Although current therapies aim to correct these imbalances to induce remission, most patients ultimately relapse, suggesting that key pathogenic mechanisms persist. Here, we identified aberrant epithelial cell death signaling as an underlying feature of IBD that arises in patients in remission and on advanced therapy. Mechanistically, nascent inflammation skewed epithelial cells into an M1-macrophage-like transcriptional state that promoted RIPK1-independent necroptotic signaling. This signaling then triggered inducible nitric oxide synthase-assisted mitochondrial apoptosis of absorptive epithelial cells and PUMA-mediated intestinal stem cell death. Thus, aberrant epithelial cell death signaling represents a hallmark of IBD that occurs early in mucosal lesion development, persists despite current therapeutic strategies, and predicts clinical relapse.",
  "abstract_shown": true,
  "affiliations": [
    "The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia",
    "University of Melbourne, Parkville, VIC, Australia",
    "Parkville, VIC 305, Australia",
    "Parkville, VIC 3052, Australia",
    "The Walter and Eliza Hall Institute of Medical Research",
    "University of Melbourne",
    "Department of Medicine, University of Melbourne, Parkville, VIC, Australia",
    "Royal Melbourne Hospital, Parkville, VIC, Australia",
    "Department of Medicine, University of Melbourne",
    "Parkville, VIC 052, Australia",
    "Royal Melbourne Hospital",
    "New York, NY 1006, USA",
    "Pediatric Hematology/Oncology, Weill Cornell Medical College",
    "Pediatric Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA",
    "College of Life Sciences, Nankai University",
    "Tianjin, 300071, China",
    "College of Life Sciences, Nankai University, Tianjin, China",
    "Department of Biological Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea",
    "Royal Children's Hospital",
    "Royal Children’s Hospital, Parkville, VIC, Australia",
    "Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University",
    "Clinical Research Center for Pediatric Infection and Immunity, and Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University",
    "Guangzhou, 510623, China",
    "The Third Affiliated Hospital of Zhengzhou University",
    "Zhengzhou, 450052, China",
    "Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia",
    "Clinical Research Center for Pediatric Infection and Immunity, and Department of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University; Guangzhou, China",
    "The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China",
    "Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931, Cologne, Germany",
    "Centre for Cell Death, Cancer and Inflammation, UCL Cancer Institute, University College London WC1E 6BT, London, United Kingdom",
    "Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany",
    "Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, Cologne, Germany",
    "Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany",
    "Centre for Cell Death, Cancer and Inflammation, UCL Cancer Institute, University College London, London, UK",
    "Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research",
    "Clayton, VIC 3168, Australia",
    "Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia",
    "Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia",
    "Department of Molecular and Translational Science, Monash University, Clayton, VIC, Australia"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 54,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3,
        4,
        5
      ],
      "name": "Jiyi Pang",
      "orcid": "0000-0003-1680-7274"
    },
    {
      "affs": [
        6,
        7,
        0,
        1,
        8,
        9,
        2,
        3,
        10,
        4,
        5
      ],
      "name": "Aysha Al‐Ani",
      "orcid": "0000-0002-4735-5234"
    },
    {
      "affs": [
        0,
        3,
        4
      ],
      "name": "Komal M. Patel",
      "orcid": "0000-0003-2976-7638"
    },
    {
      "affs": [
        0,
        3,
        4
      ],
      "name": "Yunzhuo Zhou",
      "orcid": "0000-0003-3827-8916"
    },
    {
      "affs": [
        0,
        11,
        12
      ],
      "name": "Samuel N. Young",
      "orcid": "0009-0001-6543-1851"
    },
    {
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      "name": "Jinjin Chen",
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        5
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      "name": "Isabella Y. Kong",
      "orcid": "0000-0002-7480-4525"
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      "name": "Marilou H. Barrios",
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      "name": "James A. Rickard"
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      "name": "Siqi Chen",
      "orcid": "0000-0002-9498-3823"
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      "name": "Xiuquan Ma",
      "orcid": "0000-0001-7227-1289"
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    {
      "affs": [
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      "name": "Farzaneh‐Sadat Rezazadeh‐Shojaee",
      "orcid": "0000-0003-1194-7550"
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      "name": "Seong-Beom Kim",
      "orcid": "0009-0003-7658-6693"
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      "name": "Siavash Foroughi",
      "orcid": "0000-0001-6916-8424"
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      "name": "Wayne Cawthorne",
      "orcid": "0009-0001-8467-8091"
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      "name": "Annette V. Jacobsen",
      "orcid": "0000-0003-0252-7685"
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      "name": "Asha Jois",
      "orcid": "0000-0003-3966-1183"
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      "name": "Ashley L. Weir",
      "orcid": "0000-0002-3072-2616"
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    {
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      "name": "Lachlan W. Whitehead",
      "orcid": "0000-0002-4388-9642"
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        21,
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      "name": "Pradeep Rajasekhar",
      "orcid": "0000-0002-1983-7244"
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    {
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      "name": "Christopher R. Horne",
      "orcid": "0000-0003-1318-514X"
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      "name": "Ruqian Lyu",
      "orcid": "0000-0002-7736-6612"
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        3,
        10
      ],
      "name": "Lucy J. Mather"
    },
    {
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        10
      ],
      "name": "Raymond K. H. Yip",
      "orcid": "0000-0003-2698-7686"
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    {
      "affs": [
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        8,
        9,
        3,
        10
      ],
      "name": "Ellen Tsui",
      "orcid": "0009-0005-7340-7412"
    },
    {
      "affs": [
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        10
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      "name": "Imadh Abdul Azeez",
      "orcid": "0000-0002-1661-1872"
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      "name": "Tao Tan",
      "orcid": "0000-0001-5924-4112"
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      "name": "Weiwei Liang",
      "orcid": "0009-0000-1187-8095"
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        3,
        10
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      "name": "Suresh Sivanesan",
      "orcid": "0009-0006-1595-6701"
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      "affs": [
        6,
        7,
        28
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      "name": "Andrew Metz",
      "orcid": "0000-0002-1544-7783"
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      "affs": [
        6,
        7,
        29,
        28
      ],
      "name": "Ashwin Patwardhan",
      "orcid": "0000-0001-5656-4356"
    },
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      "affs": [
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        7,
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        22,
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      ],
      "name": "Natalie Shea"
    },
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      "affs": [
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        2,
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        4,
        5
      ],
      "name": "Guru Iyngkaran",
      "orcid": "0000-0002-0486-9585"
    },
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      "affs": [
        6,
        7,
        3,
        4
      ],
      "name": "Daniel Schneider",
      "orcid": "0000-0002-4404-6567"
    },
    {
      "affs": [
        6,
        7,
        11,
        12
      ],
      "name": "Alexander Thomas Elford",
      "orcid": "0000-0001-6144-1369"
    },
    {
      "affs": [
        6,
        7,
        2,
        3,
        4,
        5
      ],
      "name": "William Beattie",
      "orcid": "0000-0002-4970-969X"
    },
    {
      "affs": [
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      "name": "Finlay Macrae"
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      "name": "Gianmaria Liccardi",
      "orcid": "0000-0002-2662-1281"
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      "name": "Henning Walczak",
      "orcid": "0000-0002-6312-4591"
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      "name": "Yuxia Zhang",
      "orcid": "0000-0003-2715-0925"
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      "name": "Oliver M. Sieber",
      "orcid": "0000-0001-9480-0786"
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      "name": "Tim D. Spelman",
      "orcid": "0000-0001-9204-3216"
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      "affs": [
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        5
      ],
      "name": "Lisa G. Giulino-Roth",
      "orcid": "0000-0002-6040-8644"
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      "name": "Michael Christie",
      "orcid": "0000-0001-8006-6832"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunshun Chen",
      "orcid": "0000-0003-4911-5653"
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        0,
        1
      ],
      "name": "Kelly L. Rogers",
      "orcid": "0000-0002-6755-0221"
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      "name": "Rory J. Bowden",
      "orcid": "0000-0001-8596-0366"
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      "name": "Sandra E. Nicholson",
      "orcid": "0000-0002-1314-2134"
    },
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      "affs": [
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        0
      ],
      "name": "Kate E. Lawlor",
      "orcid": "0000-0003-0471-6842"
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      ],
      "name": "Edwin D. Hawkins",
      "orcid": "0000-0002-3686-8261"
    },
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        0,
        1
      ],
      "name": "Britt Christensen",
      "orcid": "0000-0002-8746-4275"
    },
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      "affs": [
        0,
        1
      ],
      "name": "André L. Samson",
      "orcid": "0000-0002-0637-2716"
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        0,
        1
      ],
      "name": "James Edward Vince",
      "orcid": "0000-0001-7166-2798"
    },
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      ],
      "name": "James M. Murphy",
      "orcid": "0000-0003-0195-3949"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/37fxp64t4cth9.bib",
  "cited_by": 10,
  "doi": "10.1126/science.aeh7112",
  "fulltext_url": null,
  "id": "37fxp64t4cth9",
  "issns": [
    "0036-8075",
    "0193-4511",
    "1095-9203"
  ],
  "landing_url": "https://doi.org/10.1126/science.aeh7112",
  "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": [
    [
      "openalex",
      "2715|Inflammatory Bowel Disease"
    ]
  ],
  "openalex": "W4404345740",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "42658927",
  "published": "2026-08-27",
  "publisher": "American Association for the Advancement of Science",
  "ris": "https://research.draconitic.com/paper/37fxp64t4cth9.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T13:20:39Z",
      "native_id": "W4404345740",
      "source": "openalex",
      "url": "https://doi.org/10.1126/science.aeh7112"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2715|Inflammatory Bowel Disease",
      "subfield": "general"
    }
  ],
  "title": "A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease",
  "title_text": "A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:39Z",
  "url": "https://research.draconitic.com/paper/37fxp64t4cth9",
  "venue": "Science",
  "versions": []
}