Wu Qingsi, Nie Jia, Gao Yayi, Xu Peng, Sun Qijuan, Yang Jing, Han Lei, Chen Zuojia, Wang Xiuwen, Lv Ling, Tsun Andy, Shen Jijia, Li Bin
Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032, China.
Department of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China.
Sci Rep. 2015 Nov 9;5:16355. doi: 10.1038/srep16355.
T helper 17 (Th17) cells not only play critical roles in protecting against bacterial and fungal infections but are also involved in the pathogenesis of autoimmune diseases. The retinoic acid-related orphan receptor (RORγt) is a key transcription factor involved in Th17 cell differentiation through direct transcriptional activation of interleukin 17(A) (IL-17). How RORγt itself is regulated remains unclear. Here, we report that p300, which has histone acetyltransferase (HAT) activity, interacts with and acetylates RORγt at its K81 residue. Knockdown of p300 downregulates RORγt protein and RORγt-mediated gene expression in Th17 cells. In addition, p300 can promote RORγt-mediated transcriptional activation. Interestingly, the histone deacetylase (HDAC) HDAC1 can also interact with RORγt and reduce its acetylation level. In summary, our data reveal previously unappreciated posttranslational regulation of RORγt, uncovering the underlying mechanism by which the histone acetyltransferase p300 and the histone deacetylase HDAC1 reciprocally regulate the RORγt-mediated transcriptional activation of IL-17.
辅助性T细胞17（Th17）不仅在抵抗细菌和真菌感染中发挥关键作用，还参与自身免疫性疾病的发病机制。维甲酸相关孤儿受体（RORγt）是一种关键转录因子，通过直接转录激活白细胞介素17A（IL-17）参与Th17细胞分化。RORγt自身如何被调控仍不清楚。在此，我们报道具有组蛋白乙酰转移酶（HAT）活性的p300与RORγt相互作用并使其K81残基乙酰化。敲低p300可下调Th17细胞中RORγt蛋白和RORγt介导的基因表达。此外，p300可促进RORγt介导的转录激活。有趣的是，组蛋白去乙酰化酶（HDAC）HDAC1也可与RORγt相互作用并降低其乙酰化水平。总之，我们的数据揭示了RORγt此前未被认识的翻译后调控，揭示了组蛋白乙酰转移酶p300和组蛋白去乙酰化酶HDAC1相互调节RORγt介导的IL-17转录激活的潜在机制。
