Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital to Nanjing University, Nanjing, China.
Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
Sci Rep. 2017 Jan 17;7:40531. doi: 10.1038/srep40531.
Efficient presentation of alien antigens triggers activation of T lymphocytes and robust host defense against invading pathogens. This pathophysiological process relies on the expression of major histocompatibility complex (MHC) molecules in antigen presenting cells such as macrophages. Aberrant MHC II transactivation plays a crucial role in the pathogenesis of atherosclerosis. Class II transactivator (CIITA) mediates MHC II induction by interferon gamma (IFN-γ). CIITA activity can be fine-tuned at the post-translational level, but the mechanisms are not fully appreciated. We investigated the role of protein arginine methyltransferase 1 (PRMT1) in this process. We report here that CIITA interacted with PRMT1. IFN-γ treatment down-regulated PRMT1 expression and attenuated PRMT1 binding on the MHC II promoter. Over-expression of PRMT1 repressed MHC II promoter activity while PRMT1 depletion enhanced MHC II transactivation. Mechanistically, PRMT1 methylated CIITA and promoted CIITA degradation. Therefore, our data reveal a previously unrecognized role for PRMT1 in suppressing CIITA-mediated MHC II transactivation.
有效呈现异源抗原会触发 T 淋巴细胞的激活，并对入侵病原体产生强大的宿主防御。这个病理生理过程依赖于主要组织相容性复合体（MHC）分子在抗原呈递细胞（如巨噬细胞）中的表达。异常的 MHC II 反式激活在动脉粥样硬化的发病机制中起着至关重要的作用。II 类转录激活物（CIITA）通过干扰素γ（IFN-γ）介导 MHC II 的诱导。CIITA 的活性可以在翻译后水平上进行微调，但机制尚不完全清楚。我们研究了蛋白质精氨酸甲基转移酶 1（PRMT1）在这个过程中的作用。我们在这里报告，CIITA 与 PRMT1 相互作用。IFN-γ 处理下调 PRMT1 的表达，并减弱 PRMT1 在 MHC II 启动子上的结合。PRMT1 的过表达抑制 MHC II 启动子活性，而 PRMT1 的耗竭增强 MHC II 的反式激活。在机制上，PRMT1 甲基化 CIITA 并促进 CIITA 降解。因此，我们的数据揭示了 PRMT1 在抑制 CIITA 介导的 MHC II 反式激活中的一个以前未被认识的作用。
