TRPM2 Deficiency Attenuates Allergic Rhinitis-Like Inflammation by Modulating Ca2+-NFAT Signaling and Treg Responses

Allergic rhinitis (AR) is a widespread chronic inflammatory condition causing nasal itching, sneezing, and congestion, significantly impacting quality of life. Current therapeutic options often provide suboptimal efficacy for many patients, and long-term use can lead to adverse effects. Understanding novel molecular targets is crucial for developing more effective treatments. This study investigates the role of transient receptor potential melastatin 2 (TRPM2) in AR, focusing on its influence on T cell function, Th2 inflammatory responses, Treg/Th17 balance, and upstream Ca2+-NFAT signaling pathways.

Researchers investigated the role of TRPM2 in an ovalbumin (OVA)-induced allergic rhinitis model using TRPM2 knockout mice compared to wild-type (WT) controls. The study integrated behavioral assessments to quantify clinical symptoms, histopathological analyses for nasal inflammation, and immunological assays to evaluate immune cell differentiation and cytokine levels. Further mechanistic insights were gained through qPCR to measure gene expression and Western blotting to assess protein levels, specifically focusing on Ca2+-NFAT signaling pathways.

TRPM2 knockout mice exhibited significantly reduced clinical symptoms and nasal inflammation compared to WT controls. They also showed lower serum OVA-specific IgE levels and decreased expression of key inflammatory cytokines, including IL-4, IL-5, and IL-33. This suggests a broad dampening of the Th2 immune response. Furthermore, TRPM2 deficiency was associated with an expansion of Treg cells, indicating a shift towards immune tolerance. Mechanistically, the knockout mice displayed reduced Ca2+ influx, decreased NFATc1 nuclear translocation, and lower IL-2 production, highlighting the involvement of the Ca2+-NFAT pathway. Although IL-17 expression was reduced, the decrease in Th17 cell frequency did not reach statistical significance. These findings collectively point to TRPM2 as a critical mediator in OVA-induced AR-like inflammation.

TRPM2 knockout mice exhibited significantly reduced clinical symptoms and nasal inflammation, alongside lower serum OVA-specific IgE levels and decreased expression of key inflammatory cytokines, including IL-4, IL-5, and IL-33.