Dermatophagoides Pteronyssinus 1 Facilitates the Epithelial-Mesenchymal Transition of Nasal Mucosa Epithelial Cells to Impair Epithelial Barrier Function by Promoting NF-κB-Mediated Regulatory T Cells Differentiation and Interleukin-10 Secretion

Abstract

Background: Regulatory T cells (Treg) effectively impact allergic rhinitis (AR), the underpinning mechanism of which still warrants investigation. The predominant mite allergen, Dermatophagoides pteronyssinus 1 (Der p1), is the primary inducing factor for AR. Therefore, our study aims to explore whether Der p1 can induce AR by regulating Treg. Methods: The AR mouse model was established by exposure to Dermatophagoides pteronyssinus 1 (Der p1). The behaviors and pathological alterations in the nasal mucosa tissues of mice were assessed, and biochemical indexes of mouse serum were examined. Determination concerning the functions of nasal mucosal epithelial barrier as well as the expressions of epithelial-mesenchymal transition (EMT)/inflammation-related factors was achieved using Western blot, fluorescein isothiocyanate-dextran (FD4) assay, and enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to determine the proportion of Treg in peripheral blood mononuclear cells (PBMCs). Furthermore, the conditioned medium of PBMCs treated with Der p1 (CM-Der p1) or nuclear factor-kappaB (NF-κB) inhibitors (CM-Der p1-NI) was used to culture nasal mucosal epithelial cells (NMECs), and then the vitality, barrier function, and EMT in NMECs were tested. Results: Der p1 increased the frequency of rubbing and sneezing in mice, allergy-related biochemical indexes in serum, and interleukin (IL)-4, IL-6, and IL-10 levels in PBMCs (p < 0.001). Moreover, Der p1 increased the proportion of eosinophil infiltration in the nasal mucosa, impaired epithelial barrier function, EMT, NF-κB activation, and Treg differentiation (p < 0.01). However, these effects of Der p1 were reversed by NF-κB inhibitors (p < 0.05). Interestingly, NMECs cultured in CM-Der p1-NI showed higher viability, less IL-10 secretion, repaired barrier function, and inhibited EMT compared to the NMECs cultured in CM-Der p1 (p < 0.05). Conclusions: Der p1 may stimulate IL-10 secretion through NF-κB pathway-mediated Treg differentiation, thereby inducing EMT in NMECs to impair epithelial barrier function.