022 UHRF1 downregulation promotes T follicular helper cell differentiation by increasing BCL6 expression in SLE

Background: Transcription factor B cell lymphoma 6 (BCL6) is a master regulator of T follicular helper (Tfh) cells, which play crucial role in the pathogenesis systemic lupus erythematosus (SLE). However, mechanisms by BCL6 expression regulated are poorly understood. Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) an important epigenetic that regulates DNA methylation histone modifications. In present study, we assessed whether UHRF1 can regulate influence differentiation proliferation Tfh cells. Results: Compared to healthy controls, mean fluorescence intensity (UHRF1-MFI) cells from SLE patients was significantly downregulated, whereas (BCL6-MFI) upregulated. vitro, knockdown led overexpression promoted differentiation. contrast, downregulation decreased vivo, conditional gene knockout (UHRF1-cKO) mouse revealed depletion enhance proportion induce augmented GC reaction mice treated NP-keyhole limpet hemocyanin (NP-KLH). Mechanistically, decrease H3K27 trimethylation (H3K27me3) levels promoter region Conclusions: Our results demonstrated leads increased decreasing H3K27me3 levels, promoting vitro vivo. This finding reveals regulating provides potential target for therapy.