The Rhinology Department, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China.
Academy of Medical Science, Zhengzhou University, Zhengzhou, 450052, China.
Hum Cell. 2021 May;34(3):800-807. doi: 10.1007/s13577-021-00496-1. Epub 2021 Feb 7.
T helper (Th) 2 cell-medicated immune response participates in various immune diseases, including systemic lupus erythematosus (SLE). Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to be associated with T helper 2 (Th2) cell activation. Here, we demonstrated the molecular mechanism of NEAT1 in regulating Th2 cell activation. We found that NEAT1 was located in nucleus. NEAT1 overexpression promoted the levels of Th2-related cytokines IL-4, IL-5 and IL-13 in CD4 T cells. Moreover, NEAT1 up-regulation reduced Th1-related cytokine INF-γ production and enhanced the levels of Th17-related cytokines IL-17 in CD4 T cells. STAT6 deficiency reduced the levels of IL-4, IL-5, IL-13 and IL-17 enhanced the levels of INF-γ in CD4 T cells, which was rescued by NEAT1 overexpression. Moreover, NEAT1 promoted STAT6 protein expression, whereas NEAT1 had no effect on the expression of STAT6 mRNA. Furthermore, NEAT1 interacted with STAT6, inhibited the ubiquitination of STAT6 in CD4 T cells. In conclusion, our work has confirmed that NEAT1 promotes STAT6 expression by inhibiting STAT6 ubiquitination, thereby promoting Th2 cell activation. Thus, our work may highlight novel insights into the molecular mechanism of NEAT1 in regulating Th2 cell activation.
辅助性 T 细胞（Th）2 细胞介导的免疫反应参与各种免疫疾病，包括系统性红斑狼疮（SLE）。长链非编码 RNA 核斑组装转录本 1（NEAT1）已被报道与辅助性 T 细胞 2（Th2）细胞激活有关。在这里，我们展示了 NEAT1 调节 Th2 细胞激活的分子机制。我们发现 NEAT1 位于细胞核内。NEAT1 的过表达促进了 CD4 T 细胞中 Th2 相关细胞因子 IL-4、IL-5 和 IL-13 的水平。此外，NEAT1 的上调减少了 Th1 相关细胞因子 INF-γ的产生，并增加了 CD4 T 细胞中 Th17 相关细胞因子 IL-17 的水平。STAT6 缺陷降低了 CD4 T 细胞中 IL-4、IL-5、IL-13 和 IL-17 的水平，增加了 INF-γ的水平，而过表达 NEAT1 则挽救了这一现象。此外，NEAT1 促进了 STAT6 蛋白的表达，而对 STAT6 mRNA 的表达没有影响。此外，NEAT1 与 STAT6 相互作用，抑制了 CD4 T 细胞中 STAT6 的泛素化。总之，我们的工作证实了 NEAT1 通过抑制 STAT6 泛素化促进 STAT6 表达，从而促进 Th2 细胞激活。因此，我们的工作可能突出了 NEAT1 调节 Th2 细胞激活的分子机制的新见解。
