Yang Yang, Tang Qian, Zhao Ming, Liang Gongping, Wu Haijing, Li Duo, Xie Yubing, Tan Yixin, Dai Yong, Yung Susan, Chan Tak Mao, Lu Qianjin
Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Changsha Blood Center, Changsha, Hunan, China.
Clin Immunol. 2015 May;158(1):67-76. doi: 10.1016/j.clim.2015.03.005. Epub 2015 Mar 17.
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease involving multiple organs and characterized by overproduction of autoantibodies and T and B cell abnormalities. The treatment for SLE has been restricted to immunosuppressants and corticosteroids. Mycophenolate mofetil (MMF), as a relatively new immunosuppressant, is now widely used in the treatment of SLE patients, particularly those with nephritis. However, it is unclear whether mycophenolic acid (MPA) could modulate the reported disorders of epigenetic status in CD4(+)T cells from SLE patients. In this study, we demonstrated that MPA can upregulate the histone H3/H4 global acetylation status by regulating HATs and HDACs in lupus CD4(+)T cells. Furthermore, we found that MPA also affected the histone H4 acetylation and histone H3K4 tri-methylation levels in CD40L promoter region that inhibited the expression of CD40L. These findings indicate the potential epigenetic mechanism of therapeutic effects of MPA in SLE.
系统性红斑狼疮（SLE）是一种复杂的系统性自身免疫性疾病，累及多个器官，其特征是自身抗体过度产生以及T细胞和B细胞异常。SLE的治疗一直局限于免疫抑制剂和皮质类固醇。霉酚酸酯（MMF）作为一种相对较新的免疫抑制剂，目前广泛用于治疗SLE患者，尤其是患有肾炎的患者。然而，尚不清楚霉酚酸（MPA）是否能调节SLE患者CD4(+)T细胞中报道的表观遗传状态紊乱。在本研究中，我们证明MPA可通过调节狼疮CD4(+)T细胞中的组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（HDACs）来上调组蛋白H3/H4的整体乙酰化状态。此外，我们发现MPA还影响CD40L启动子区域的组蛋白H4乙酰化和组蛋白H3K4三甲基化水平，从而抑制CD40L的表达。这些发现表明MPA在SLE中治疗作用的潜在表观遗传机制。
