{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:18:28Z","timestamp":1792225108254,"version":"4.4.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Allergic rhinitis (AR) is an underrecognized contributor to olfactory dysfunction (OD). Although smell loss in AR is commonly attributed to conductive obstruction, some patients exhibit persistent or disproportionate hyposmia despite improvement in nasal congestion, suggesting that additional sensorineural mechanisms may exist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>We hypothesize that, in a subset of patients with persistent, moderate-to-severe, type 2-high AR-associated OD without macroscopic olfactory cleft obstruction, allergen-induced epithelial stress in the olfactory cleft may activate an alarmin\u2013ILC2\/type 2 neuroimmune pathway. IL-33 and thymic stromal lymphopoietin (TSLP) released from epithelial or sustentacular cell populations, together with IL-25 and lipid mediator signals from tuft-like microvillar cells, may engage group 2 innate lymphoid cells (ILC2s) as early amplifiers within a broader type 2 inflammatory network. This response is proposed to contribute to three candidate injury modules: IL-13\/STAT6-associated horizontal basal cell fate bias, IL-5\/eosinophil-associated olfactory sensory neuron injury, and IL-4\/IL-13-associated sustentacular cell dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Rationale and evidence gap<\/jats:title>\n                    <jats:p>Current support is indirect and derives from murine olfactory inflammation models, ex vivo olfactory preparations, human non-olfactory nasal mucosal studies, and chronic rhinosinusitis with nasal polyps (CRSwNP) studies used as mechanistic analogies. None of the proposed mechanisms has been directly validated in human AR olfactory cleft tissue, which together represent the central evidence gap.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications<\/jats:title>\n                    <jats:p>The model generates falsifiable predictions regarding olfactory cleft alarmins, type 2 cytokines, ILC2-like immune niches, basal cell transcriptional state, and biomarker-linked responses in future proof-of-mechanism studies. It is presented as a hypothesis to guide future non-invasive biomarker studies, ethically feasible tissue analyses, organoid experiments, and biomarker-enriched proof-of-mechanism trials, not as a validated disease mechanism or current treatment recommendation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1867859","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:57:05Z","timestamp":1783490225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The alarmin\u2013ILC2 axis as a candidate mechanism for persistent olfactory dysfunction in allergic rhinitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jin-xiang","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Zhongshan Hospital of Traditional Chinese Medicine, Affiliated to Guangzhou University of Chinese 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