ABSTRACT

This study examined the potential roles of CC10 (Clara cell 10-kD protein) and ILC2s (type 2 innate lymphoid cells) in allergic rhinitis (AR). After ovalbumin was used to construct the AR model, microarray analysis was performed to reveal the key differentially expressed genes. The phenotypic changes of nasal mucosa were examined by H&E staining. Western blot analysis, qRT-PCR, ELISA and immunohistochemistry were performed to identify the levels of cytokines. The lineage markers (CD127 and CD117) of ILC2s were detected using immunofluorescence. The microarray analysis and qRT-PCR results showed that CC10 overexpression inhibited the expression of A20, BAFF, and IL-4 R in vivo. Also, CC10 overexpression was found to ameliorate the damage of nasal mucosa in AR mice. Investigations revealed that the ILC2s were activated in AR mice and AR patients with high levels of IgE, IgG1, IL-4, IL-5, IL-13, IL-25, and IL-33. Moreover, CD127+ was found to activate ILC2s. However, CC10 overexpression suppressed the activation of ILC2s. In conclusion, this research suggested that CC10 could suppress the activation of ILC2s to attenuate the damage of nasal mucosa and that CD127+ may be a biomarker of the activation of ILC2s in AR mice and AR patients.

摘要

本研究探讨了 CC10（Clara 细胞 10-kD 蛋白）和 ILC2s（2 型先天淋巴细胞）在过敏性鼻炎 (AR) 中的潜在作用。在使用卵清蛋白构建AR模型后，进行微阵列分析以揭示关键的差异表达基因。H&E染色检测鼻黏膜表型变化。进行蛋白质印迹分析、qRT-PCR、ELISA和免疫组织化学以确定细胞因子的水平。使用免疫荧光检测 ILC2 的谱系标记（CD127 和 CD117）。微阵列分析和 qRT-PCR 结果表明，CC10 过表达抑制体内A20、BAFF 和 IL-4 R 的表达. 此外，发现 CC10 过表达可改善 AR 小鼠鼻粘膜的损伤。研究表明，ILC2 在 IgE、IgG1、IL-4、IL-5、IL-13、IL-25 和 IL-33 水平高的 AR 小鼠和 AR 患者中被激活。此外，发现 CD127+ 可激活 ILC2。然而，CC10 过表达抑制了 ILC2 的激活。总之，本研究表明CC10可以抑制ILC2s的激活以减轻鼻粘膜损伤，CD127+可能是AR小鼠和AR患者ILC2s激活的生物标志物。