The effect of mycophenolic acid on epigenetic modifications in lupus CD4+T cells

- MPA increases the histone H3/H4 global acetylation by enhancing HATs level.
- MPA upregulates the histone H3/H4 global acetylation by decreasing HDACs level.
- MPA decreases the histone H4 acetylation level in CD40L promoter region.
- MPA downregulates the histone H3K4 tri-methylation level in CD40L promoter region.

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.