It is well known that DNA methylation is mediated by DNMTs but is protected by MBD (39, 40), In the present study, we also found that the hypermethylation occurred in the Smad7 gene promoter (-1000 to +2000) in human peripheral RA CD4+ T cells, which was associated with increased DNMT1, but not DNMT3A and DNMT3B, while suppressing MBD4 but not MBD2 expression by CD4+ T cells. The gene discussed is MBD4; the disease is rheumatoid arthritis.