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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.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1948935","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:49:39Z","timestamp":1791359379000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TL1A morphological shifts and inflammatory heterogeneity in rhinosinusitis and allergic rhinitis: a hypothesis-driven review"],"prefix":"10.3389","volume":"17","author":[{"given":"Tianwei","family":"Pei","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Dalian No.3 People\u2019s Hospital","place":["Dalian, Liaoning, 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