{
  "abstract": "Chronic rhinosinusitis with nasal polyps (CRSwNP) affects 1%-4% of adults globally and imposes a substantial burden on quality of life. Despite endoscopic surgery, topical corticosteroids, and systemic glucocorticoids, postoperative recurrence exceeds 54% at five years. Even with the advent of biologics targeting downstream type 2 effectors, such as dupilumab, mepolizumab, and omalizumab, a meaningful subset of patients, particularly those with mixed or non-type 2 endotypes, remains inadequately controlled. The epithelial alarmins thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25) occupy the apex of the inflammatory cascade, functioning as proximal triggers that bridge innate barrier disruption to adaptive type 2 amplification. This review examines the shared and distinctive pathobiology of these three molecules in CRSwNP, compares the clinical trajectories of tezepelumab (Phase 3), anti-IL-33/ST2 agents (Phase 2/3), and emerging anti-IL-25 biologics (early-phase), and outlines a conceptual framework for future investigation. We propose that upstream alarmin inhibition offers a broader immunomodulatory scope than downstream cytokine blockade, yet its clinical translation hinges on three unresolved challenges: overcoming functional redundancy among alarmins, defining the long-term safety profile of sustained epithelial-immune suppression, and validating clinically accessible predictive biomarkers. The proposed algorithms and biomarker cut-offs remain exploratory and require prospective validation in CRSwNP-specific cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Otolaryngology, Mianyang Central Hospital/The Affiliated Mianyang Hospital of University of Electronic Science and Technology"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shuhua Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8zdq3rq90knce.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1970480",
  "fulltext_url": "https://europepmc.org/articles/PMC13693526",
  "id": "8zdq3rq90knce",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1970480/full",
  "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",
      "2733|Sinusitis and nasal conditions"
    ]
  ],
  "openalex": "W7221105823",
  "pdf_url": "https://europepmc.org/articles/PMC13693526?pdf=render",
  "pmcid": "PMC13693526",
  "pmid": "42921522",
  "published": "2026-10-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8zdq3rq90knce.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1970480",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1970480/full"
    },
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42921522",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921522"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Targeting upstream alarmins (TSLP, IL-33, IL-25): a new frontier in treating type 2 chronic rhinosinusitis with nasal polyps",
  "title_text": "Targeting upstream alarmins (TSLP, IL-33, IL-25): a new frontier in treating type 2 chronic rhinosinusitis with nasal polyps",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/8zdq3rq90knce",
  "venue": "Frontiers in Immunology",
  "versions": []
}