{
  "abstract": "Background: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental toxicants, yet the toxicological mechanisms by which they induce idiopathic pulmonary fibrosis (IPF) remain poorly understood. This study aims to systematically elucidate the molecular basis and cellular interplay driving PAH-induced pulmonary fibrosis.\n\nMethods: We first evaluated the toxicological profiles of 16 priority-controlled PAHs using toxicological databases and then conducted in vitro experiments to assess their effects on pulmonary epithelial cells. By integrating transcriptomic data, we combined differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Mendelian randomization (MR) to screen IPF-associated genes. Given the well-defined structure of IL1R2, molecular docking and molecular dynamics (MD) simulations were employed to evaluate the binding affinity and conformational stability of the 16 PAHs with IL1R2. Finally, using single-cell transcriptomics, we compared the functional disparities between IL1R2-positive and IL1R2-negative macrophages within the fibrotic microenvironment.\n\nResults: In vitro , PAHs exerted cytotoxic effects on pulmonary epithelial cells, manifested primarily as suppressed cell viability, dysregulated inflammatory cytokine expression, and DNA damage. Intersecting the identified IPF-associated genes with PAH-target genes from the CTD database yielded diagnostic and prognostic models, ultimately pinpointing SPP1, IL1R2, and SCGB3A2 as core targets. Molecular docking and MD simulations demonstrated stable binding of the 16 PAHs to IL1R2. Single-cell transcriptomic analysis further revealed that IL1R2-negative macrophages mediate a more pronounced pro-fibrotic phenotype via the IL-1 signaling pathway and exacerbate pro-fibrotic cell–cell communication with fibroblasts.\n\nConclusions: In summary, this study clarifies the key targets and cellular mechanisms underlying PAH-mediated respiratory toxicity, providing a multidimensional research strategy for the risk assessment of environmental pollutant-induced pulmonary fibrosis.",
  "abstract_shown": true,
  "affiliations": [
    "Hefei Cancer Hospital of Chinese Academy of Sciences (CAS), Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences",
    "Science Island Branch, Graduate School of University of Science and Technology of China",
    "Department of General Surgery (Hepatobiliary Surgery), Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital",
    "Burns Department, General Hospital of Taiyuan Iron and Steel Group Co., Ltd; (Sixth Hospital of Shanxi Medical University)"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xin Tang"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Peiyi Bai"
    },
    {
      "affs": [
        2
      ],
      "name": "Qinyang Du"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wulin Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Gaopeng Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3sysz54wpbk4q.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1968775",
  "fulltext_url": null,
  "id": "3sysz54wpbk4q",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968775/full",
  "language": null,
  "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",
      "2740|Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis"
    ]
  ],
  "openalex": "W7223119740",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1968775/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/3sysz54wpbk4q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1968775",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968775/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Integrating multi-omics and machine learning to reveal IL1R2-driven macrophage-fibroblast spatial interactions in polycyclic aromatic hydrocarbon-induced pulmonary fibrosis",
  "title_text": "Integrating multi-omics and machine learning to reveal IL1R2-driven macrophage-fibroblast spatial interactions in polycyclic aromatic hydrocarbon-induced pulmonary fibrosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/3sysz54wpbk4q",
  "venue": "Frontiers in Immunology",
  "versions": []
}