{
  "abstract": "IntroductionDespite advances in asthma management, asthma exacerbations (AE) remain a leading cause of morbidity, and the immunopathological mechanisms driving AE progression need further clarification. Here, we explored the role of macrophage apoptosis resistance in AE using clinical samples and murine models.MethodsMacrophages were isolated from bronchoalveolar lavage fluid (BALF) of AE patients and lung macrophages from AE mice to detect Bcl-2 expression and apoptosis. We performed adoptive transfer of ex vivo apoptotic bone marrow-derived macrophages (BMDMs) and ADAM8-silenced BMDMs. Integrative transcriptomic analysis of GSE144576 combined with in vivo validation was used to screen regulators of lung macrophage apoptosis resistance. In vitro and in vivo experiments with the peptidomimetic inhibitor BK1361 were conducted to dissect ADAM8 downstream signaling.ResultsMacrophages from AE patients and AE mice showed elevated Bcl-2 and strong apoptosis resistance. Adoptive transfer of apoptotic BMDMs partially reversed macrophage apoptosis resistance and mitigated airway inflammation. Transcriptomics plus animal validation identified ADAM8 as a regulator of macrophage apoptosis resistance. Consistently, transfer of ADAM8-silenced BMDMs relieved airway inflammation and reduced apoptosis resistance. Mechanistically, ADAM8 may activate PI3K/AKT signaling to upregulate Bcl-2 and promote apoptosis resistance. BK1361 suppressed ADAM8/PI3K/AKT signaling, enhanced macrophage apoptosis, and reduced inflammatory infiltration, mucus hypersecretion, and airway hyperresponsiveness (AHR) in AE mice.DiscussionIn summary, macrophage apoptosis resistance drives inflammatory amplification in AE. The ADAM8/PI3K/AKT axis mediates this phenotype, indicating ADAM8 as a promising therapeutic target for AE.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Long Chen"
    },
    {
      "name": "Xinyu Wu"
    },
    {
      "name": "Huijun Liu"
    },
    {
      "name": "Qizhi Luo"
    },
    {
      "name": "Lin Yuan"
    },
    {
      "name": "Qiuyan Qin"
    },
    {
      "name": "Qianyu Zhao"
    },
    {
      "name": "Jia Wang"
    },
    {
      "name": "Chi Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6chf7eb710xv5.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1869233",
  "fulltext_url": null,
  "id": "6chf7eb710xv5",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1869233",
  "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": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6chf7eb710xv5.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:20:45Z",
      "native_id": "10.3389/fimmu.2026.1869233",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1869233"
    },
    {
      "first_seen": "2026-11-02T12:23:23Z",
      "native_id": "10.3389/fimmu.2026.1869233",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1869233/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "ADAM8 is associated with asthma exacerbation by promoting lung macrophages apoptosis resistance through PI3K/AKT signaling pathway",
  "title_text": "ADAM8 is associated with asthma exacerbation by promoting lung macrophages apoptosis resistance through PI3K/AKT signaling pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T00:25:32Z",
  "url": "https://research.draconitic.com/paper/6chf7eb710xv5",
  "venue": "Frontiers in Immunology",
  "versions": []
}