Interleukin-4-Mediated NLRP3 Inflammasome Activation in Microglia Contributes to Allergic Rhinitis via Central...

Area of Science:

• Neuroscience
• Immunology
• Allergy Research

Background:

• Allergic rhinitis (AR) pathogenesis is presumed to involve central sensitization, a hypersensitive state of the central nervous system.
• The specific mechanisms linking central sensitization to AR have been underexplored.
• Investigating the role of the trigeminal nucleus caudalis (TNC) in AR is crucial.

Purpose of the Study:

• To elucidate the role of central sensitization in the TNC in the pathogenesis of allergic rhinitis (AR).
• To investigate the contribution of microglial neuroinflammation and Interleukin-4 (IL-4) to central sensitization in AR.
• To identify potential therapeutic targets for AR by understanding these mechanisms.

Main Methods:

• An ovalbumin-induced AR mouse model was utilized.
• Electrophysiological recordings and immunofluorescence assessed TNC neuron activation.
• Chemogenetics, pharmacological inhibition of microglia, and in vitro co-culture systems were employed to study mechanisms.

Main Results:

• AR mice exhibited increased TNC neuronal excitability and central sensitization markers.
• Inhibition of TNC neurons or microglia ameliorated AR symptoms and neuroinflammation.
• IL-4 promoted pro-inflammatory microglia activation and NLRP3 inflammasome-mediated IL-1β production in the TNC.

Conclusions:

• Microglial neuroinflammation-induced central sensitization in the TNC is a key mechanism contributing to AR.
• IL-4 plays a critical role in activating microglia and promoting neuroinflammation in AR.
• Targeting TNC-mediated central sensitization and microglial activation presents a promising therapeutic strategy for AR.