Abstract：
Allergic rhinitis (AR) is a common allergic disease. Cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) is a member of the cytochrome P450 family of enzymes, while its role in AR is still unveiled. In AR mice, T cell-specific overexpression of Cyp2e1 relieved the AR symptoms. Overexpressed-Cyp2e1 restrained the infiltration of eosinophils and mast cells in the nasal mucosa of mice, and the inflammatory cells in nasal lavage fluid (NALF). Cyp2e1 overexpressed mice exhibited decreased goblet cell hyperplasia and mucus secretion as well as decreased MUC5AC expression in nasal mucosa. The epithelial permeability and integrity of nasal mucosa were improved upon Cyp2e1 overexpression in AR mice, as evidenced by decreased fluorescein isothiocyanate-dextran 4 content in serum, increased expression of IL-25, IL-33, and TSLP in NALF, and increased expression of ZO-1 and occluding in nasal mucosa. Cyp2e1 inhibited Th2 immune response by decreasing the expression and secretion of IL-4, IL-5, and IL-13 as well as the expression of GATA-3 in NALF or nasal mucosa. We proved that Cyp2e1 inhibited the differentiation of naïve CD4+ T cells toward the Th2 subtype, which was regulated by MAFB by binding to Cyp2e1 promoter to activate its transcription. Overall, these results show the potential role of Cyp2e1 in alleviating AR symptoms by restraining CD4+ T cells to Th2 cell differentiation. Our findings provide further insight into the AR mechanism.
摘要：
变应性鼻炎(AR)是一种常见的过敏性疾病。细胞色素P450，家族2，亚家族e，多肽1（Cyp2e1）是细胞色素P450酶家族的成员，虽然它在AR中的作用仍在揭晓。在AR小鼠中，Cyp2e1的T细胞特异性过表达缓解了AR症状。过表达Cyp2e1抑制小鼠鼻黏膜嗜酸性粒细胞和肥大细胞的浸润,和鼻腔灌洗液（NALF）中的炎症细胞。Cyp2e1过表达小鼠的杯状细胞增生和粘液分泌减少，鼻粘膜中MUC5AC表达减少。Cyp2e1过表达后，AR小鼠鼻黏膜上皮通透性和完整性得到改善，血清中异硫氰酸荧光素-葡聚糖4含量降低，NALF中IL-25，IL-33和TSLP的表达增加，鼻粘膜中ZO-1的表达和阻塞增加。Cyp2e1通过降低NALF或鼻粘膜中IL-4，IL-5和IL-13的表达和分泌以及GATA-3的表达来抑制Th2免疫应答。我们证明Cyp2e1抑制了初始CD4+T细胞向Th2亚型的分化，通过与Cyp2e1启动子结合激活其转录而受MAFB调控。总的来说,这些结果表明Cyp2e1通过抑制CD4+T细胞向Th2细胞分化来缓解AR症状的潜在作用。我们的发现为AR机制提供了进一步的见解。
