Evidence map›Paper›PMID 40336088›Full record

ArticleCell communication and signaling : CCS2025

Accumulation of long-chain unsaturated fatty acids in the airway inflammatory microenvironment drives eosinophil etosis and corticosteroid resistance.

Yurong Bai, Pengda Fang, Shasha Li, Zhenhao Xiao, Wenyi Chen, Wenlong Li, Xinyue Wang, Jingyuan Chen, Yue Li, Junhai Chen and 6 more

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In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
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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

16 authors.

Yurong Bai *Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Pengda Fang *Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Shasha Li *Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
Zhenhao Xiao *Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Wenyi ChenDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Wenlong LiDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Xinyue WangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Jingyuan ChenDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Yue LiDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Junhai ChenDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Weiqiang HuangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Xin LuoDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China.
Shigeharu UekiDepartment of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, 010-8543, Japan.
Deyu FangDepartment of Pathology, Northwestern University Feinberg School Medicine, Chicago, IL, 60611, USA.
Qintai YangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China. Yangqint@mail.sysu.edu.cn.
Yana ZhangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangdong, Guangzhou, 510630, Guangdong, China. Zhangyn95@mail.sysu.edu.cn.

Funding

the Key-area Research and Development Program of Guangdong Province 2020B0101130015the National Natural Science Foundation of China 82371121, 82171114, 82271148, U20A20399the Natural Science Foundation of Guangdong Province 2022A1515011787, 2021A1515011764the Science and Technology Program of Guangzhou 202201020402, 2024A04J6570
6 · The paper itself

Abstract

backgroundEosinophilic inflammation is a feature of chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with eosinophilic CRSwNP (ENP) tend to be refractory and prone to recurrence. Although there is increasing evidence linking lipid metabolic irregularities to eosinophilia, the particular lipid responsible for promoting eosinophilic inflammation and the precise molecular mechanisms involved remain unclear.

methodsLipidomic atlas and metabolic pathway enrichment were identified by liquid chromatography-tandem mass spectrometry and RNA sequencing, respectively. Eosinophil extracellular trap cell death (EETosis) was detected by immunofluorescence microscopy and transmission electron microscopy. Functional analyses were performed on purified eosinophils.

resultsThe unbiased lipidomic atlas identified a specific accumulation in long-chain fatty acids (LCFAs) in ENP. Consistently, RNA-seq analysis confirmed the enrichment in long-chain unsaturated fatty acid metabolism pathway in ENP. In this lipid-rich airway inflammatory environment, EETosis including ETotic eosinophils, EETs release and Charcot-Leyden crystals (CLCs) generation was enhanced in ENP, and associated with disease severity. Further, we found that both saturated and unsaturated LCFAs, such as arachidonic acid, are critical fuel sources to trigger eosinophil activation and filamentous DNA release, whereas only arachidonic acid could induce crystalline Galectin10 (CLCs). Mechanistically, arachidonic acid induces EETosis through a mechanism independent of reactive oxygen species but the IRE1α/XBP1s/PAD4 pathway. Both the long-acting dexamethasone and short-acting hydrocortisone, while facilitate eosinophil apoptosis, are ineffective to block arachidonic acid-induced EETosis.

conclusionsOur findings demonstrate a previously unknown role of the LCFA arachidonic acid in mediating EETosis and glucocorticoid insensitivity to drive ENP progression, which may lead to novel insights regarding the treatment of patients with refractory eosinophilic inflammation.

Indexed as

Adrenal Cortex HormonesCellular MicroenvironmentDrug ResistanceEosinophilsFatty Acids, UnsaturatedInflammationExtracellular TrapsHumansNasal PolypsSinusitisAdrenal Cortex HormonesFatty Acids, UnsaturatedEndoplasmic reticulumEosinophil extracellular trap cell deathGlucocorticoid insensitivityLong-chain fatty acidsProtein arginine deiminase 4

Identifiers

PMID40336088
PMCPMC12057054

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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 OpenQuestion graph.