PLIN2 exacerbates Allergic Rhinitis by inhibiting PINK1/Parkin-mediated mitophagy

To investigate the pro-inflammatory role and underlying mechanism of Perilipin 2 (PLIN2) in Allergic Rhinitis (AR), focusing on its regulation of PINK1/Parkin-mediated mitophagy and the subsequent impact on lipid metabolism and oxidative stress.

Single-cell RNA sequencing (scRNA-seq) analysis was performed using GSE261706 from the GEO database, involving nasal mucosa from AR patients and healthy controls. A murine AR model was induced by ovalbumin (OVA), and human nasal epithelial cells (HNEpCs) were stimulated with Der p1. Interventions included AAV-mediated PLIN2 knockdown in vivo and siRNA-mediated knockdown in vitro. Techniques included Western blotting, qRT-PCR, flow cytometry, ELISA, and immunofluorescence/histological staining to assess PLIN2 expression, mitophagy, lipid accumulation, oxidative stress, and inflammatory responses.

scRNA-seq analysis identified PLIN2 as a significantly upregulated gene in AR epithelial cells, which correlated with dysfunctional autophagy pathways. In both OVA-induced mice and Der p1-treated HNEpCs, PLIN2 expression was significantly elevated, accompanied by inhibited mitophagy (decreased LC3-II/I ratio, reduced PINK1/Parkin levels, and p62 accumulation), increased lipid deposition, and elevated ROS levels. PLIN2 knockdown markedly ameliorated AR pathology in mice, reducing inflammatory infiltration and serum levels of IgE, IL-4, and IL-5. Mechanistically, PLIN2 knockdown restored PINK1/Parkin-mediated mitophagy, decreased lipid accumulation, and attenuated ROS-induced cellular damage in HNEpCs.

PLIN2 exacerbates AR pathogenesis by inhibiting PINK1/Parkin-mediated mitophagy, promoting lipid accumulation and oxidative stress, and ultimately causing cellular damage in nasal epithelial cells. PLIN2 acts as a pivotal mediator linking metabolic dysregulation to inflammation, highlighting it as a promising therapeutic target for AR treatment.