{
  "abstract": "Extracellular vesicles (EVs) mediate intercellular communication, yet whether extracellular phospholipid metabolism on EV membranes regulates immune activation remains incompletely understood. Through comparative phenotypic analyses of multiple secreted phospholipase A2 (sPLA2)-deficient mouse strains, we identified PLA2G12A as a stromal regulator of extracellular lipid metabolism that promotes IgE/antigen-dependent mast cell activation. Pla2g12a deficiency attenuated passive cutaneous and systemic anaphylaxis and selectively impaired IgE-dependent, but not IgE-independent, mast cell responses. Single-cell RNA-sequencing of mouse and human skin revealed that PLA2G12A is expressed in broad subsets of stromal fibroblasts, including papillary fibroblasts adjacent to mast cells, implicating a specialized stromal niche in mast cell regulation. Consistently, mast cell-intrinsic PLA2G12A was dispensable, whereas fibroblast-targeted deletion of Pla2g12a phenocopied global Pla2g12a deficiency. Lipidomic analyses during IgE-mediated anaphylaxis revealed a significant reduction in lysophospholipids, accompanied by minimal changes in oxylipins, in Pla2g12a-deficient skin. Mechanistically, fibroblast-derived PLA2G12A hydrolyzed phospholipids in EV-enriched fractions to generate multiple lysophospholipids, and treatment with either the PLA2G12A-treated EV-enriched fraction or exogenous lysophospholipids restored impaired IgE-dependent anaphylactic responses in Pla2g12a-deficient mice. Collectively, these findings establish sPLA2-driven extracellular phospholipid remodeling as a mechanism by which stromal niches regulate allergic inflammation.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine (CDBIM), Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan",
    "Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan",
    "Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan",
    "Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City 230-0045, Kanagawa, Japan",
    "Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shiba-koen, Minato-ku, Tokyo 105-8512, Japan",
    "Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q), Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yoshitaka Taketomi",
      "orcid": "0000-0003-4094-9846"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yoshimi Miki"
    },
    {
      "affs": [
        0
      ],
      "name": "Takayoshi Higashi"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuki Nagasaki",
      "orcid": "0000-0002-4717-6877"
    },
    {
      "affs": [
        2
      ],
      "name": "Kuniyuki Kano"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Makoto Arita"
    },
    {
      "affs": [
        2
      ],
      "name": "Junken Aoki"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Makoto Murakami",
      "orcid": "0000-0002-4565-6017"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7jnbrmytjcct3.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15201848",
  "fulltext_url": "https://europepmc.org/articles/PMC13702701",
  "id": "7jnbrmytjcct3",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/20/1848",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2403|Mast cells and histamine"
    ]
  ],
  "openalex": "W7221531194",
  "pdf_url": "https://europepmc.org/articles/PMC13702701?pdf=render",
  "pmcid": "PMC13702701",
  "pmid": "42929821",
  "published": "2026-10-12",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/7jnbrmytjcct3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15201848",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/20/1848"
    },
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42929821",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42929821"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Mast cells and histamine",
      "subfield": "immunology"
    }
  ],
  "title": "Fibroblast-Derived PLA2G12A Amplifies Mast Cell Activation Through Extracellular Phospholipid Remodeling",
  "title_text": "Fibroblast-Derived PLA2G12A Amplifies Mast Cell Activation Through Extracellular Phospholipid Remodeling",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/7jnbrmytjcct3",
  "venue": "Cells",
  "versions": []
}