{
  "abstract": "Aims\n\nAutoimmune pancreatitis (AIP) is a representative manifestation of IgG4-related disease characterized by lymphoplasmacytic inflammation and storiform fibrosis. Although epigenetic dysregulation has been implicated in autoimmune diseases, its contribution to the pathogenesis of AIP remains unclear.Methods and results\n\nGenome-wide DNA methylation profiling was performed using the Infinium MethylationEPIC array in tissues affected by AIP and obstructive pancreatitis (OP). Differentially methylated regions (DMRs) were identified and subjected to pathway enrichment analysis. Among the significantly enriched gene sets, GNF2_INPP5D showed the strongest enrichment and was selected for further investigation. INPP5D promoter methylation was analyzed, and its protein expression was evaluated by immunohistochemistry. Single-cell RNA sequencing (scRNA-seq) was performed to identify the cells expressing INPP5D. Pathway enrichment analysis showed significant enrichment of the INPP5D-associated immune-regulatory network in AIP. Promoter-associated CpG probes within the INPP5D locus showed predominant hypomethylation in AIP compared with the findings in OP (adjusted p < 0.05). In contrast, immunohistochemistry demonstrated reduced INPP5D expression in spindle-shaped stromal macrophage/histiocyte-lineage cells in AIP tissues. scRNA-seq analysis identified INPP5D expression predominantly in C1QC-positive macrophages and lymphocytes.Conclusions\n\nAIP is characterized by epigenetic remodeling of the INPP5D-associated immune-regulatory network accompanied by reduced INPP5D expression in stromal macrophage-lineage cells. These findings provide evidence for an association between altered INPP5D-related epigenetic regulation and the characteristic fibro-inflammatory microenvironment of AIP. INPP5D may represent a candidate biomarker and a potential therapeutic target in IgG4-related disease.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. tuehara@shinshu-u.ac.jp.",
    "Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.",
    "Department of Laboratory Medicine, Nagano Children's Hospital, Azumino, Japan.",
    "Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.",
    "Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.",
    "Department of Biomedical Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Takeshi Uehara",
      "orcid": "0000-0002-7694-9015"
    },
    {
      "affs": [
        1
      ],
      "name": "Mai Iwaya"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Shiho Asaka"
    },
    {
      "affs": [
        1
      ],
      "name": "Tomoyuki Nakajima"
    },
    {
      "affs": [
        1
      ],
      "name": "Shotaro Komamura"
    },
    {
      "affs": [
        3
      ],
      "name": "Hiroshi Sawaguchi"
    },
    {
      "affs": [
        3
      ],
      "name": "Shunsuke Imamura"
    },
    {
      "affs": [
        3
      ],
      "name": "Akira Nakamura"
    },
    {
      "affs": [
        4
      ],
      "name": "Shinsuke Sugenoya"
    },
    {
      "affs": [
        4
      ],
      "name": "Akira Shimizu"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Hiroyoshi Ota"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cqc7jy4kxv8t4.bib",
  "cited_by": 0,
  "doi": "10.1186/s12876-026-05170-0",
  "fulltext_url": "https://europepmc.org/articles/PMC13685243",
  "id": "cqc7jy4kxv8t4",
  "issns": [
    "1471-230X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42902176",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC799-869"
    ],
    [
      "openalex",
      "2745|IgG4-Related and Inflammatory Diseases"
    ]
  ],
  "openalex": "W7171088401",
  "pdf_url": "https://europepmc.org/articles/PMC13685243?pdf=render",
  "pmcid": "PMC13685243",
  "pmid": "42902176",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/cqc7jy4kxv8t4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42902176",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42902176"
    },
    {
      "first_seen": "2026-10-30T13:46:06Z",
      "native_id": "c5e7e9d4452441519d49c67dbfa0c7bc",
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      "url": "https://doi.org/10.1186/s12876-026-05170-0"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|IgG4-Related and Inflammatory Diseases",
      "subfield": "general"
    }
  ],
  "title": "Epigenetic regulation of INPP5D and its downstream molecular network in autoimmune pancreatitis.",
  "title_text": "Epigenetic regulation of INPP5D and its downstream molecular network in autoimmune pancreatitis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:06Z",
  "url": "https://research.draconitic.com/paper/cqc7jy4kxv8t4",
  "venue": "BMC gastroenterology",
  "versions": []
}