MiR-155 overexpression regulates Th1/Th2 balance by inhibiting BACH1 to activate Nrf-2/HO-1 signaling pathway in allergic rhinitis

Allergic rhinitis (AR) is a common respiratory inflammatory disease characterized by Th2 inflammatory response from exposure to allergens. The current study aimed to explore the underlying mechanism of miR-155 in AR. Nasal mucosa tissue samples and nasal lavage fluid samples were obtained from patients diagnosed with AR and healthy subjects who served as the control. We found that the miR-155 expression was downregulated in AR patients while the expression of BACH1 was upregulated. miR-155 overexpression reduced apoptosis, the levels of IL-4 and IL-12 in AR nasal epithelial cells (NECs). CD4+T cells were treated with supernatant of NECs following miR-155 overexpression. miR-155 up-regulation elevated the ratio of Th1/Th2, reduced the levels of IL-4 and IL-5, elevated the levels of IFN-gamma and IL-12 in CD4+T cells. Down-regulation of SOCS1 and SOCS3, upregulation of SOCS4, SOCS5 and SOCS6 were observed in CD4+T cells following treatment of NECs with miR-155 overexpression. Mechanically speaking, miR-155 activated Nrf2/HO-1 signaling pathway by interacting with BACH1. miR-155 elevated Th1/Th2 proportion in CD4+T cells by activating Nrf2/HO-1 signaling pathway. Moreover, an AR mouse model was also constructed, the frequency of sneezing, nose rubbing, and rhinorrhea were elevated. After treatment with miR-155 agomir, these symptoms were significantly alleviated. In conclusion, this work showed that miR-155 activated Nrf2/HO-1 signaling pathway by targeting BACH1, thereby affecting Th1/Th2 balance in AR. Our findings suggest that miR-155 could hold promise as a novel AR therapy.