{
  "abstract": "Lipogenesis-driven metabolic flux is crucial for differentiation of pathogenic Th17 cells. Although our previous CRISPR-based screening identified PLA2G12A as a key player in this process, it has remained obscure how this secreted phospholipase A 2 isoform controls Th17 differentiation. Here we show that global, T cell-specific, or fibroblast-specific deletion of PLA2G12A prevents Th17 differentiation and associated diseases including psoriasis and arthritis. PLA2G12A acts on Th17-derived extracellular vesicles (EVs) to produce lysophospholipids including the RORγt activator 1-oleoyl-lysophosphatidylethanolamine. These lysophospholipids are further converted by autotaxin to lysophosphatidic acid (LPA), which assists Th17 differentiation mainly via LPA 2 receptor. Moreover, PLA2G12A promotes the secretion and uptake of EVs by Th17 cells and alters their cargo contents. Defective Th17 differentiation by PLA2G12A deficiency is rescued by supplementation with PLA2G12A-modified EVs. Importantly, a PLA2G12A-blocking antibody prevents Th17 differentiation and ameliorates psoriasis and arthritis models. Thus, targeting the PLA2G12A-EV-lysophospholipid axis may be useful for treatment of Th17-related diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan",
    "Calpain Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan",
    "Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8654, Japan",
    "Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan",
    "Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan",
    "Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan",
    "Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan",
    "RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan",
    "Division of Metabolomics, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan",
    "Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA",
    "Department of Innovative Medical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan",
    "Department of Innovative Medical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan; Department of Regulation of Infectious Cancers, Division of Cellular and Molecular Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan",
    "Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 260-8670, Japan. Electronic address: makmurak@m.u-tokyo.ac.jp"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chika Mochizuki-Ono"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoshitaka Taketomi",
      "orcid": "0000-0003-4094-9846"
    },
    {
      "affs": [
        1
      ],
      "name": "Atsushi Irie"
    },
    {
      "affs": [
        2
      ],
      "name": "Kuniyuki Kano",
      "orcid": "0000-0002-4539-5750"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuki Nagasaki",
      "orcid": "0000-0002-4717-6877"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoshimi Miki",
      "orcid": "0000-0002-8587-0333"
    },
    {
      "affs": [
        3
      ],
      "name": "Takashi Ono"
    },
    {
      "affs": [
        4
      ],
      "name": "Yasumasa Nishito",
      "orcid": "0000-0001-7621-6172"
    },
    {
      "affs": [
        5
      ],
      "name": "Takahiro Nakajima",
      "orcid": "0000-0002-4937-5378"
    },
    {
      "affs": [
        6
      ],
      "name": "Yuri Tomabechi",
      "orcid": "0000-0001-5208-163X"
    },
    {
      "affs": [
        6
      ],
      "name": "Kazuharu Hanada",
      "orcid": "0000-0002-5998-1849"
    },
    {
      "affs": [
        6
      ],
      "name": "Mikako Shirouzu",
      "orcid": "0000-0002-7997-2149"
    },
    {
      "affs": [
        7
      ],
      "name": "Takashi Watanabe"
    },
    {
      "affs": [
        8
      ],
      "name": "Kosuke Hata",
      "orcid": "0000-0002-2278-4796"
    },
    {
      "affs": [
        8
      ],
      "name": "Yoshihiro Izumi",
      "orcid": "0000-0003-4608-4652"
    },
    {
      "affs": [
        8
      ],
      "name": "Takeshi Bamba",
      "orcid": "0000-0002-7442-2738"
    },
    {
      "affs": [
        9
      ],
      "name": "Jerold J. M. Chun",
      "orcid": "0000-0003-3964-0921"
    },
    {
      "affs": [
        10
      ],
      "name": "Kai Kudo",
      "orcid": "0000-0002-5410-3334"
    },
    {
      "affs": [
        11
      ],
      "name": "Ai Kotani",
      "orcid": "0000-0002-0976-8687"
    },
    {
      "affs": [
        5
      ],
      "name": "Yusuke Endo",
      "orcid": "0000-0002-7223-1938"
    },
    {
      "affs": [
        2
      ],
      "name": "Junken Aoki",
      "orcid": "0000-0001-9435-1896"
    },
    {
      "affs": [
        12
      ],
      "name": "Makoto Murakami",
      "orcid": "0000-0002-4565-6017"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b29gvk2p53nm4.bib",
  "cited_by": 6,
  "doi": "10.1016/j.celrep.2026.117391",
  "fulltext_url": null,
  "id": "b29gvk2p53nm4",
  "issns": [
    "2211-1247",
    "2639-1856"
  ],
  "landing_url": "https://doi.org/10.1016/j.celrep.2026.117391",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "2403|Psoriasis: Treatment and Pathogenesis"
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  "openalex": "W7163212425",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "42229421",
  "published": "2026-06-01",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/b29gvk2p53nm4.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T13:21:11Z",
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      "url": "https://doi.org/10.1016/j.celrep.2026.117391"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Psoriasis: Treatment and Pathogenesis",
      "subfield": "immunology"
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  ],
  "title": "PLA2G12A-driven extracellular vesicle-lipid signaling amplifies pathogenic T cell responses in inflammatory diseases",
  "title_text": "PLA2G12A-driven extracellular vesicle-lipid signaling amplifies pathogenic T cell responses in inflammatory diseases",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:11Z",
  "url": "https://research.draconitic.com/paper/b29gvk2p53nm4",
  "venue": "Cell Reports",
  "versions": []
}