Work

Stromal-derived Anxa1 engages neutrophil Fpr2 to brake the Nlrp3 inflammasome in otitis media with effusion

Year: 2026

Type: article

Abstract: Uncontrolled neutrophilic inflammation and Nlrp3 inflammasome activation contribute to a wide range of mucosal disorders, yet the endogenous circuits that constrain this process at the cellular level remain poorly defined. Using single-cell RNA sequencing of the Eustachian tube in a rat model of ovalbumin-induced otitis media with effusion (OME), we identified massive neutrophil infiltration coupled with intrinsic Nlrp3 inflammasome activation as dominant features of the early OME microenvironment. Systematic intercellular communication analysis using CellChat predicted a disease-specific Annexin A1 (Anxa1)–formyl peptide receptor 2 (Fpr2) ligand-receptor axis converging on infiltrating neutrophils. Intratympanic pre-treatment with Anxa1 dose-dependently suppressed Nlrp3, IL-1β, and IL-18 without altering the priming cytokine TNF-α, reduced middle ear effusion volume on micro-CT, and preserved ciliary and goblet cell architecture. Co-administration of the Fpr2 antagonist WRW4 reversed the Anxa1-mediated reduction in IL-18 and middle ear effusion, indicating that the Anxa1-Fpr2 axis functions as an Fpr2-dependent checkpoint that limits inflammasome amplification rather than initial inflammatory priming. These findings identify a pharmacologically tractable, neutrophil-targeted brake on the Nlrp3 inflammasome and provide a mechanism-based direction for local anti-inflammatory therapy in OME.

Source: Scientific Reports

DOI: 10.1038/s41598-026-75348-9