Nonylphenol Exacerbates Allergic Rhinitis in Vitro and Mice

In previous studies, we verified that nonylphenols (NPs) facilitate the occurrence of allergic rhinitis (AR). By analyzing data from the Gene Expression Omnibus database and subsequent verification with clinical samples, we confirmed that the A3SS alternative splicing of TRAF2 and NCK-interacting kinase (TNIK) plays a significant role in AR. Meanwhile, we discovered that NP could suppress the expression of hnRNPUL1 and increase the alternative splicing ratio of TNIK in the nasal mucosa of mice. Further studies revealed that downregulation of the splicing factor hnRNPUL1 promoted A3SS alternative splicing in TNIK, leading to the deposition of β-catenin in nasal mucosa tissue and enhanced binding of β-catenin with TCF1 and TCF4. This binding, in turn, increased the cell ratio of Th2 cells, decreased the ratio of Th1 and Treg cells, and shifted the Th1/Th2 ratio in favor of Th2, driving the immune response toward Th2 cell proliferation and differentiation. A mere increase in β-catenin expression sufficiently promoted promotes general proliferation but does not drive subset differentiation. Under NP intervention, the expression of hnRNPUL1 was reduced, Th2 proliferation and differentiation in local tissues were more pronounced, and symptoms in mice were more severe than under non-NP intervention. These findings confirm that NP intake can interfere with the transcription process and exacerbate the development of AR.