UHRF1 downregulation promotes T follicular helper cell differentiation by increasing BCL6 expression in SLE.
UHRF1 downregulation promotes T follicular helper cell differentiation by increasing BCL6 expression in SLE.
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UHRF1 下调通过增加 SLE 中 BCL6 的表达促进滤泡辅助 T 细胞分化
DOI：
10.1186/s13148-021-01007-7
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发表时间：
2021-02-10
影响因子：
5.7
通讯作者：
Zhao M
中科院分区：
文献类型：
--
作者：
Liu L;Hu L;Yang L;Jia S;Du P;Min X;Wu J;Wu H;Long H;Lu Q;Zhao M
BackgroundTranscription factor B cell lymphoma 6 (BCL6) is a master regulator of T follicular helper (Tfh) cells, which play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanisms by which BCL6 expression is regulated are poorly understood. Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an important epigenetic factor that regulates DNA methylation and histone modifications. In the present study, we assessed whether UHRF1 can regulate BCL6 expression and influence the differentiation and proliferation of Tfh cells.ResultsCompared to healthy controls, the mean fluorescence intensity of UHRF1 (UHRF1-MFI) in Tfh cells from SLE patients was significantly downregulated, whereas that of BCL6 (BCL6-MFI) was significantly upregulated. In vitro, UHRF1 knockdown led to BCL6 overexpression and promoted Tfh cell differentiation. In contrast, UHRF1 overexpression led to BCL6 downregulation and decreased Tfh cell differentiation. In vivo, conditional UHRF1 gene knockout (UHRF1-cKO) in mouse T cells revealed that UHRF1 depletion can enhance the proportion of Tfh cells and induce an augmented GC reaction in mice treated with NP-keyhole limpet hemocyanin (NP-KLH). Mechanistically, UHRF1 downregulation can decrease DNA methylation and H3K27 trimethylation (H3K27me3) levels in theBCL6 promoter region of Tfh cells.ConclusionsOur results demonstrated that UHRF1 downregulation leads to increased BCL6 expression by decreasing DNA methylation and H3K27me3 levels, promoting Tfh cell differentiation in vitro and in vivo. This finding reveals the role of UHRF1 in regulating Tfh cell differentiation and provides a potential target for SLE therapy.
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影响因子：
1.2
作者：
Klarquist, Jared;Janssen, Edith M.
通讯作者：
Janssen, Edith M.
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影响因子：
8.6
作者：
Huang, Xin;Wu, Haijing;Lu, Qianjin
通讯作者：
Lu, Qianjin
影响因子：
4.4
作者：
Qi, Shanshan;Li, Yongkui;Wang, Zheng
通讯作者：
Wang, Zheng
脂肪来源的间充质干细胞成骨细胞分化过程中DLX3，ATF4和FRA1基因的启动子甲基化和表达模式。
DOI：
10.34172/bi.2020.31
发表时间：
2020
期刊：
BioImpacts : BI
影响因子：
--
作者：
Rahimzadeh S;Rahbarghazi R;Aslani S;Rajabi H;Latifi Z;Farshdousti Hagh M;Nourazarian A;Nozad Charoudeh H;Nouri M;Abhari A
通讯作者：
Abhari A
影响因子：
2.5
作者：
Banica, Leontina M.;Besliu, Alina N.;Matache, Cristiana
通讯作者：
Matache, Cristiana