Increased miR-124-3p alleviates type 2 inflammatory response in allergic rhinitis via IL-4Rα

Background and objectives miRNAs play a crucial role in regulating immune responses.

However, the effect of miR-124-3p on type 2 inflammation in allergic rhinitis (AR) is unclear.

We aimed to study the immune regulation of miR-124-3p in AR and the mechanisms involved.

Methods The direct interaction between miR-124-3p and IL-4Rα was confirmed through a dual-luciferase reporter assay.

In vitro splenic lymphocytes from mice and peripheral blood mononuclear cells (PBMCs) from healthy individuals were cultured and treated with miR-124-3p mimic/inhibitor.

Twenty-four female C57BL/C mice were divided into four groups: control, AR model, miR-124-3p agomir, and miR-124-3p antagomir groups ( n  = 6 per group).

The allergic responses were evaluated based on the number of sneezing and nasal scratching, the serum HDM-specific IgE (sIgE) levels, and the degree of nasal mucosa eosinophil infiltration.

The expression of IL-4Rα, p-STAT6, and type 2 inflammatory cytokines (IL-4, IL-5 and IL-13) in lymphocytes or nasal mucosa was determined by qPCR, western blotting, flow cytometry, immunohistochemistry and immunofluorescence.

Results miR-124-3p directly targets the 3'UTR of IL-4Rα.

The miR-124-3p mimic lowered the IL-4Rα, p-STAT6, IL-4, IL-5, and IL-13 expression levels in both mouse splenic lymphocytes and human PBMCs in vitro, and the miR-124-3p inhibitor rescued these changes.

Furthermore, the miR-124-3p agomir decreased the levels of IL-4Rα and IL-4 in nasal mucosa, Th2 differentiation in spleen, and allergic response in AR mice.

Moreover, the miR-124-3p antagonist increased the IL-4Rα and IL-4 levels and further aggravated the allergic responses.

Conclusions miR-124-3p might attenuate type 2 inflammation in AR by regulating IL-4Rα signaling, and miR-124-3p may be a promising new target in AR treatment.