Evidence mapPaperPMID 42488624Full record

ReviewFrontiers in immunology2026

The alarmin-ILC2 axis as a candidate mechanism for persistent olfactory dysfunction in allergic rhinitis.

Jin-Xiang Zhu, Hao-Ran Luo, Dan Li, Biao-Qing Lu, Wei-Juan Zhang, Guan-Jiang Huang, Yan Ruan

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Jin-Xiang ZhuDepartment of Otorhinolaryngology Head and Neck Surgery, Zhongshan Hospital of Traditional Chinese Medicine, Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, Guangdong, China.
Hao-Ran LuoThe First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Dan LiDepartment of Otorhinolaryngology, Shenzhen Traditional Chinese Medicine, Shenzhen, Guangdong, China.
Biao-Qing LuDepartment of Otorhinolaryngology Head and Neck Surgery, Zhongshan Hospital of Traditional Chinese Medicine, Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, Guangdong, China.
Wei-Juan ZhangDepartment of Otorhinolaryngology, Shaoguan Traditional Chinese Medicine, Shaoguan, Guangdong, China.
Guan-Jiang HuangDepartment of Otorhinolaryngology Head and Neck Surgery, Zhongshan Hospital of Traditional Chinese Medicine, Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, Guangdong, China.
Yan RuanDepartment of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: 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. Hypothesis: 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-ILC2/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. Rationale and evidence gap: 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. Implications: 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.

Indexed as

AlarminsLymphocytesOlfaction DisordersRhinitis, AllergicAnimalsCytokinesHumansImmunity, InnateOlfactory MucosaAlarminsCytokinesalarminallergic rhinitishorizontal basal cellsIL-33ILC2olfactory cleftolfactory dysfunctionsensorineural

Identifiers

PMID42488624
PMCPMC13388388

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.