In the present study, we demonstrated that UHRF1 regulates DNA methylation and H3K27me3 in the BCL6 promoter regions of Tfh cells, suggesting that UHRF1 downregulation promotes Tfh cell differentiation by decreasing the levels of DNA methylation and H3K27me3 in the BCL6 promoter in SLE. Here, BCL6 is linked to systemic lupus erythematosus.