hnRNPUL1-AS

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 expression of GATA3 and decreased that of Th1 cell transcription factor T-bet and Treg cell transcription factor Foxp3, driving the immune response towards Th2 polarization. A mere increase in β-catenin expression sufficiently promoted the proliferation of all helper T cell subsets; however, it did not induce any changes in Th cell differentiation. Under NP intervention, the expression of hnRNPUL1 was more reduced, Th2 polarization in local tissues was 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.