{
  "abstract": "Autoimmune uveitis (AU) is a leading cause of irreversible blindness driven by pathogenic T helper 17 (TH17) cell-mediated inflammation, yet current therapies are limited by efficacy and side effects, with immunometabolic mechanisms remaining poorly defined. By integrating single-cell RNA sequencing and multilayered metabolomic profiling in patients with AU and experimental AU models, we identified the lipid-sensing G protein-coupled receptor GPR183 as a key immunometabolic regulator in pathogenic CD4⁺ T cells. Upon activation, GPR183 modulates intracellular signaling via suppression of cyclic adenosine monophosphate-cAMP-dependent protein kinase activity and promotion of son-of-sevenless-dependent KRAS activation, which in turn elicits copper overload-induced mitochondrial oxidative stress, structural impairment, and metabolic rewiring toward glycolysis, thereby promoting TH17 cell pathogenicity. For clinical translation, virtual screening of Food and Drug Administration-approved drugs coupled with molecular docking and microscale thermophoresis validation identified fluvoxamine (FLV) as a direct GPR183 antagonist. In in vivo and in vitro uveitis and colitis models, FLV attenuated GPR183-KRAS signaling, dampened pathogenic TH17 cell responses, and alleviated tissue inflammation. These findings delineate a unique GPR183-KRAS-mitochondrial damage axis governing TH17-driven autoimmunity and support repurposing FLV as a translatable therapeutic approach for AU and other autoimmune inflammatory disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.",
    "State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.",
    "Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.",
    "Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection With TCM, Chengdu, Sichuan 610000, China."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chun Zhang",
      "orcid": "0000-0002-4183-4816"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiuxing Liu",
      "orcid": "0000-0001-5855-6624"
    },
    {
      "affs": [
        0
      ],
      "name": "Nanwei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuehan Gao"
    },
    {
      "affs": [
        2
      ],
      "name": "Chenyang Gu",
      "orcid": "0009-0008-6022-3341"
    },
    {
      "affs": [
        1
      ],
      "name": "Xinyue Shen"
    },
    {
      "affs": [
        1
      ],
      "name": "Junying Wu"
    },
    {
      "affs": [
        3
      ],
      "name": "Xuejing Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Pei Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuxuan He",
      "orcid": "0009-0005-7932-321X"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhuping Xu",
      "orcid": "0000-0002-1270-9602"
    },
    {
      "affs": [
        2
      ],
      "name": "Wenru Su",
      "orcid": "0000-0002-0506-6362"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3tfbr8bk4t5n9.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeh8465",
  "fulltext_url": "https://europepmc.org/articles/PMC13715701",
  "id": "3tfbr8bk4t5n9",
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  "licence": "CC-BY-NC",
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      "heading",
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      "heading",
      "Immunology"
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      "heading",
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    [
      "openalex",
      "2731|Ocular Diseases and Behçet’s Syndrome"
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  "pdf_url": "https://europepmc.org/articles/PMC13715701?pdf=render",
  "pmcid": "PMC13715701",
  "pmid": "42950033",
  "published": "2026-10-28",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/3tfbr8bk4t5n9.ris",
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  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Immunology",
      "subfield": "immunology"
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  ],
  "title": "Lipid-sensing GPR183-KRAS signaling mediates TH17 autoimmunity and identifies fluvoxamine repurposing in uveitis",
  "title_text": "Lipid-sensing GPR183-KRAS signaling mediates TH17 autoimmunity and identifies fluvoxamine repurposing in uveitis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:55Z",
  "url": "https://research.draconitic.com/paper/3tfbr8bk4t5n9",
  "venue": "Science Advances",
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}