{
  "abstract": "Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are heterogeneous upper-airway inflammatory disorders in which type 2 inflammation is common but does not fully explain all clinical endotypes or treatment responses. This review synthesizes evidence on tumor necrosis factor-like ligand 1A (TL1A) and considers whether its membrane-bound (mTL1A) and soluble (sTL1A) forms could connect epithelial injury, macrophage activation, and mixed inflammatory networks. Evidence from intestinal and lower-airway models supports TL1A/DR3 signaling in several immune contexts, while sinonasal studies provide only limited, cell-specific evidence and do not yet establish local TL1A abundance, shedding dynamics, or a complete macrophage-centered feedback loop. We therefore propose a testable model in which mTL1A may support contact-dependent signaling, whereas epithelial stress and protease-mediated shedding may generate soluble TL1A with broader paracrine activity. In this framework, TL1A could cooperate with IL-33, TSLP, and IL-25 and might activate macrophage-dependent relays involving CXCL8/IL-8 and IL-1beta. Because neutrophils are generally considered indirect targets of TL1A/DR3 signaling, such relays could contribute to mixed or treatment-refractory inflammation without implying that TL1A alone is sufficient. The model provides a conceptual framework for integrating endotypic heterogeneity and identifying testable biomarkers and therapeutic hypotheses, but direct validation in human sinonasal tissue, nasal lavage fluid, and relevant experimental models remains necessary.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesiology, Dalian No.3 People’s Hospital"
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tianwei Pei"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiang Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/akm9rrrbxxh8z.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1948935",
  "fulltext_url": "https://europepmc.org/articles/PMC13683971",
  "id": "akm9rrrbxxh8z",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1948935/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": "W7220841830",
  "pdf_url": "https://europepmc.org/articles/PMC13683971?pdf=render",
  "pmcid": "PMC13683971",
  "pmid": "42909314",
  "published": "2026-10-07",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/akm9rrrbxxh8z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1948935",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1948935/full"
    },
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42909314",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909314"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "TL1A morphological shifts and inflammatory heterogeneity in rhinosinusitis and allergic rhinitis: a hypothesis-driven review",
  "title_text": "TL1A morphological shifts and inflammatory heterogeneity in rhinosinusitis and allergic rhinitis: a hypothesis-driven review",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/akm9rrrbxxh8z",
  "venue": "Frontiers in Immunology",
  "versions": []
}