Evidence map›Paper›PMID 41620621›Full record

ArticleCell communication and signaling : CCS2026

NLRP3-mediated epithelial pyroptosis involved in airway hyperresponsiveness in combined eosinophilic and neutrophilic asthma.

Min Zhang, Lei Zhao, Yishu Xue, Hang Su, Yanmei Lin, Yilin Pan, Jifei Wu, Lei Han, Yan Zhou, Wuping Bao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

1 citing paper in PubMed.

  1. Review
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

10 authors.

Min Zhang *Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
Lei Zhao *Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
Yishu Xue *Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
Hang Su *Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
Yanmei LinDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
Yilin PanDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
Jifei WuDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
Lei HanDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
Yan Zhou *Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China. zhouyan790304@163.com.
Wuping Bao *Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China. wupingbao1982@163.com.

Funding

National Natural Science Foundation of China 82270027Science and Technology Commission of Shanghai municipality 22ZR1449600Shanghai General Hospital 02.06.01.21.13Shanghai General Hospital 02.06.01.21.56Zhongnanshan Medical Foundation of Guangdong Province ZNSXS-20240002
6 · The paper itself

Abstract

backgroundAirway hyperresponsiveness (AHR) contributes to asthma pathogenesis, yet targeted therapies remain limited, especially for combined eosinophilic-neutrophilic (EOS+NEU+) inflammation.

objectiveTo investigate the role of the NOD-like receptor protein 3 (NLRP3) signalling in EOS+NEU+ asthma-associated AHR.

methodsWe prospectively enrolled 48 patients with asthma and paired with 8 healthy controls. Patients with asthma were classified as non-eosinophilic (non-EOS), eosinophilic without neutrophilic (EOS+NEU−), or EOS+NEU+ asthma mainly based on induced sputum type 2 inflammation markers. Large and small airway function, inflammatory markers, and NLRP3 expression were analysed. In vivo and in vitro models mimicking each phenotype were used to investigate the effects of inhibiting NLRP3 (MCC950 or knockout), Gasdermin D (GSDMD) (disulfiram or gene silencing), and interleukin (IL)-1β signalling (IL-1R knockout) on AHR.

resultsCompared to patients with EOS+NEU− inflammation, those with EOS+NEU+ inflammation had higher sputum eosinophils and neutrophils. Large and small airway function declined across all asthma subgroups versus controls, worsening from non-EOS to EOS+NEU− and further in EOS+NEU+. Sputum NLRP3 and IL-1β increased progressively across asthma groups and correlated positively with FeNO and sputum eosinophils, while NLRP3 positively correated with neutrophils but negatively with lung function.Meanwhile, EOS+NEU+ mice showed higher NLRP3 and IL-1β and worse small airway function than those in EOS+NEU− mice. Mimicking EOS+NEU+ inflammation in vitro, IL-13 combined with IL-17 A stimulation induced NLRP3 activation, GSDMD-N-terminal (NT) upregulation, pore formation in human bronchial epithelial cells, with IL-1β/lactate dehydrogenase (LDH) release—indicative of epithelial cell pyroptosis, more obvious than single IL-13 or IL-17 A stimulation. In vivo, NLRP3 knockout suppressed GSDMD-NT and IL-1β, alleviating AHR. In vivo and in vitro, GSDMD inhibition/silencing reduced IL-1β and LDH release, mitigating AHR, while IL-1R knockout reduced airway smooth muscle tension, also improving AHR.

conclusionsEOS+NEU+ asthma showed more severe AHR compaired with non-EOS and EOS+NEU− asthma. Enhanced NLRP3/GSDMD/IL-1β signalling in EOS+NEU+ asthma, drives more severe AHR via epithelial pyroptosis and granulocytic inflammation. Targeting NLRP3/GSDMD/IL-1β offers therapeutic potential, with sputum NLRP3 and IL-1β as promising biomarkers for risk factor of progression. CLINICAL

trial registrationChiCTR2500104677.

Indexed as

AsthmaEosinophilsEpithelial CellsNeutrophilsNLR Family, Pyrin Domain-Containing 3 ProteinPyroptosisRespiratory HypersensitivityAdultAnimalsCase-Control StudiesFemaleHumansMaleMiceMiddle AgedSputumNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanAirway hyperresponsivenessAsthmaEosinophilic-Neutrophilic inflammationEpitheliumNLRP3Pyroptosis

Identifiers

PMID41620621
PMCPMC12934062

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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.