{
  "abstract": "Chronic inflammatory skin diseases are characterized by epithelial barrier dysfunction and immune dysregulation, yet the epithelial-intrinsic mechanisms that initiate inflammation remain poorly understood. TMEM79 is a dermatitis-associated transmembrane protein expressed in keratinocytes, but how its loss promotes skin disease remains unclear. Here, using keratinocyte-specific Tmem79 conditional knockout (cKO) mice and TMEM79-deficient human keratinocytes, we find that TMEM79 is required for proper epithelial differentiation and barrier formation, and that its loss induces keratinocyte stress and ferroptosis-associated lipid peroxidation. Longitudinal analysis of neonatal and early postnatal Tmem79-deficient skin revealed disrupted epidermal homeostasis and early type I IFN signaling preceding the later emergence of type 17 inflammation. Mechanistically, genetic ablation of Sting1, but not Mavs, ameliorated dermatitis and downstream type 17 inflammation, while IL-17A was required for subsequent epidermal hyperplasia. These findings establish STING-dependent signaling as an upstream driver of skin immune activation and pathology. Together, our findings link early-life epithelial stress to innate immune activation and suggest that targeting lipid peroxidation or STING signaling may help prevent inflammatory skin disease progression.",
  "abstract_shown": true,
  "affiliations": [
    "F. M. Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School , Boston, MA ,",
    "Division of Gastroenterology, Hepatology, and Nutrition, Boston Children’s Hospital , Boston, MA ,",
    "Harvard Graduate Program in Biological and Biomedical Sciences, Harvard Medical School , Boston, MA ,",
    "Yunnan Key Laboratory of Cell Metabolism and Diseases, Center for Life Sciences, School of Life Sciences, Yunnan University ,",
    "Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA ,",
    "Program in Immunology, Harvard Medical School , Boston, MA ,",
    "Broad Institute of MIT and Harvard , Cambridge, MA ,",
    "Harvard Stem Cell Institute , Cambridge, MA ,",
    "Ragon Institute of MGH, MIT and Harvard , Cambridge, MA ,",
    "Division of Immunology, Boston Children’s Hospital, Harvard Medical School , Boston, MA ,",
    "Department of Immunology, Harvard Medical School , Boston, MA ,",
    "Gene Lay Institute of Immunology and Inflammation of Brigham and Women’s Hospital, MGH, and Harvard Medical School , Boston, MA ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mengxu Ge"
    },
    {
      "affs": [
        0
      ],
      "name": "Danilo Predes",
      "orcid": "0000-0003-1864-0324"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Andrew Kwong",
      "orcid": "0000-0002-0052-5881"
    },
    {
      "affs": [
        0
      ],
      "name": "Eunice To"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Maorong Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Aakanksha Jain"
    },
    {
      "affs": [
        4
      ],
      "name": "Wenyi Wei",
      "orcid": "0000-0003-0512-3811"
    },
    {
      "affs": [
        1,
        5,
        6,
        7,
        8
      ],
      "name": "Jose Ordovas-Montanes"
    },
    {
      "affs": [
        9
      ],
      "name": "Manuel Leyva-Castillo",
      "orcid": "0000-0001-7394-4457"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Isaac M Chiu",
      "orcid": "0000-0002-0723-4841"
    },
    {
      "affs": [
        0
      ],
      "name": "Xi He",
      "orcid": "0000-0002-8093-7981"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ewq06z643045b.bib",
  "cited_by": 0,
  "doi": "10.1093/pnasnexus/pgag361",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732302/",
  "id": "ewq06z643045b",
  "issns": [
    "2752-6542"
  ],
  "landing_url": "https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgag361/9003321",
  "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",
      "AcademicSubjects/MED00010"
    ],
    [
      "heading",
      "AcademicSubjects/SCI00010"
    ],
    [
      "heading",
      "AcademicSubjects/SOC00010"
    ],
    [
      "heading",
      "Biological, Health, and Medical Sciences"
    ],
    [
      "heading",
      "Dermatology"
    ],
    [
      "heading",
      "PNAS_Nexus/dermatology"
    ],
    [
      "openalex",
      "2708|Dermatology and Skin Diseases"
    ]
  ],
  "openalex": "W7224080074",
  "pdf_url": "https://academic.oup.com/pnasnexus/advance-article-pdf/doi/10.1093/pnasnexus/pgag361/72548091/pgag361.pdf",
  "pmcid": "PMC13732302",
  "pmid": "42984892",
  "published": "2026-10-28",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/ewq06z643045b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1093/pnasnexus/pgag361",
      "source": "crossref",
      "url": "https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgag361/9003321"
    },
    {
      "first_seen": "2026-11-08T12:22:18Z",
      "native_id": "PMC13732302",
      "source": "pmc",
      "url": "https://doi.org/10.1093/pnasnexus/pgag361"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2708|Dermatology and Skin Diseases",
      "subfield": "general"
    }
  ],
  "title": "Keratinocyte TMEM79 protects early life epidermal homeostasis and restrains STING-dependent skin inflammation",
  "title_text": "Keratinocyte TMEM79 protects early life epidermal homeostasis and restrains STING-dependent skin inflammation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:18Z",
  "url": "https://research.draconitic.com/paper/ewq06z643045b",
  "venue": "PNAS Nexus",
  "versions": []
}