Blocking Notch signalling reverses miR-155-mediated inflammation in allergic rhinitis

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• The Notch signalling pathway's role in allergic rhinitis (AR) pathogenesis is not fully understood.
• Previous research indicates Notch signalling influences Th2 immune responses.

Purpose of the Study:

• To elucidate the mechanism by which Notch signalling affects allergic rhinitis.
• To investigate the impact of Notch pathway inhibition on AR-related inflammation and immune factors.

Main Methods:

• Established a mouse model of allergic rhinitis (AR) using ovalbumin (OVA) sensitization.
• Analyzed nasal mucosa, serum, and spleen for inflammation, immune cell populations (ILC2s), and cytokine levels (ELISA).
• Quantified mRNA expression of Notch pathway components and miR-155 (qRT-PCR) and assessed human nasal epithelial cell (HNEpC) function after Notch inhibition (DAPT).

Main Results:

• AR model mice exhibited increased Th2 immune responses, OVA-specific IgE, IL-4, GATA3, NF-κB, and miR-155.
• AR was associated with a deteriorated Notch signalling pathway, evidenced by reduced Notch1, Notch2, RBPj, and Hes1 levels.
• Gamma-secretase inhibitor IX (DAPT) treatment abrogated these effects and inhibited HNEpC wound healing and proliferation.

Conclusions:

• The Notch signalling pathway is impaired in allergic rhinitis.
• Blocking the Notch pathway may alleviate miR-155-mediated inflammation in AR by regulating immune homeostasis.
• Notch pathway inhibition negatively impacts epithelial cell function, suggesting a complex role in AR pathology.