REVIEW article
Front. Immunol.
Sec. Inflammation
Pyroptosis-Immune Cell Crosstalk in Asthma: From Molecular Mechanisms to Precision Therapeutics
Provisionally accepted
- 1Affiliated Zhuhai Hospital, Southern Medical University, Zhuhai Hospital of Integrated Traditional Chinese & Western Medicine, Zhuhai 519000, Guangdong, China., Zhuhai, China
- 2Northeastern University, Boston, United States
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Asthma is a heterogeneous chronic airway disease characterized by complex inflammatory. Pyroptosis, a pro-inflammatory form of programmed cell death mediated by gasdermin (GSDM) family proteins, has recently emerged as a critical amplifier of airway inflammation and tissue remodeling in asthma. This review delineates the molecular underpinnings of pyroptosis, focusing on the roles of canonical (e.g., NLRP3-caspase-1) and non-canonical (e.g., caspase-4/5/11) inflammasome pathways, as well as the broader concept of PANoptosis. We elaborate on how the pore-forming activity of GSDMD and other GSDMs facilitates the release of potent pro-inflammatory cytokines (IL-1β, IL-18), driving pathogenic crosstalk among structural cells (epithelium), innate immune cells (macrophages, eosinophils, ILC2s), and adaptive immunity. Crucially, we contextualize pyroptosis within distinct asthma endotypes, proposing that allergen-driven, NLRP3-dominated pathways may underpin Th2-high/eosinophilic inflammation, while pollutant/viral-triggered, non-canonical/AIM2 pathways may favor Th2-low/neutrophilic phenotypes. The translational potential of targeting pyroptosis is underscored through a discussion of biomarkers (e.g., GSDMD-N, IL-18) and a comprehensive summary of preclinical and early clinical inhibitors targeting NLRP3, GSDMD, and key cytokines. By synthesizing these multifaceted roles, this review posits that a nuanced understanding of pyroptosis networks holds significant promise for pioneering endotype-specific therapeutic strategies in asthma management.
Keywords: pyroptosis, Asthma, Inflammasome, Gasdermin D, Eosinophils, IL-33, Airway Remodeling, NLRP3
Received: 17 Oct 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Ni, Huang, Chen, Chen, Huang and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zebo Jiang, zebojiang2011@163.com
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