title: The effect of mycophenolic acid on epigenetic modifications in lupus CD4+T cells.
abstract: 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.
authors: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Yang
authors: Y
authors: Yang
authors: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Qian
authors: Q
authors: Tang
authors: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Ming
authors: M
authors: Zhao
authors: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Gongping
authors: G
authors: Liang
authors: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Haijing
authors: H
authors: Wu
authors: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Duo
authors: D
authors: Li
authors: Changsha Blood Center, Changsha, Hunan, China.
authors: Yubing
authors: Y
authors: Xie
authors: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Yixin
authors: Y
authors: Tan
authors: Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
authors: Yong
authors: Y
authors: Dai
authors: Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors: Susan
authors: S
authors: Yung
authors: Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors: Tak Mao
authors: TM
authors: Chan
authors: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: qianlu5860@gmail.com.
authors: Qianjin
authors: Q
authors: Lu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000328:Adult; D040881:CD11a Antigen / Q000187:drug effects / Q000378:metabolism; D053282:CD27 Ligand / Q000187:drug effects / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D023201:CD40 Ligand / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006655:Histone Deacetylases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008745:Methylation / Q000187:drug effects; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
chemical_list: D040881:CD11a Antigen; D053282:CD27 Ligand; D004791:Enzyme Inhibitors; D006657:Histones; D012333:RNA, Messenger; D023201:CD40 Ligand; D006655:Histone Deacetylases; D009173:Mycophenolic Acid
keywords: CD4(+)T cells; CD40L; Epigenetics; Mycophenolic acid; Systemic lupus erythematosus