Effect of Blocking the OX40/OX40L Signaling Pathway by siRNA Interference on Animal Experimental Study of Allergic Rhinitis

Background: The identification of new approaches and intervention targets for the treatment of AR is urgently needed. We aimed to investigate the effect of blocking the OX40/OX40L signaling pathway by small interfering RNA (siRNA) on ovalbumin (OVA)-induced AR in a mouse model.

Methods: After establishment of the AR model, the mice were interfered by siRNA-OX40L (experimental group), siRNA-C (negative control group), or PBS (control group). Nose scratching, sneezing and nasal discharge were observed. OX40L mRNA and protein and the IL-5, TNF-α, regulatory T cell (Treg) -specific marker Foxp3, and eosinophil (EOS) levels were analyzed.

Results: The numbers of nose scratching and sneezing were significantly lower in the siRNA-OX40L-treated group (p <0.05). After the intervention of siRNA-OX40L, OX40L mRNA and protein levels were significantly inhibited (p <0.05), but the Foxp3 level was significantly increased in the experimental group (p <0.05). The IL-5 and TNF-α levels were significantly lower in the experimental group (p <0.05), and the reduction was more evident for the Th2-type cytokine IL-5 than for the Th1-type cytokine TNF-α. Few or no EOSs were found in the nasal mucosal epithelium of the experimental group (p <0.05), whereas EOS infiltration was significant in the other two groups.

Conclusions: Blockage of the OX40/OX40L signaling pathway with siRNA-OX40L interference can inhibit allergic reactions and relieve allergic symptoms in AR mice. The underlying mechanism may be related to correcting Th2 immune deviation, inducing immune tolerance, and promoting Treg production.