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Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus.
Nature Communications ( IF 16.6 ) Pub Date : 2018-03-19 , DOI: 10.1038/s41467-018-03530-3
Junli Liu , Xinfang Huang , Shumeng Hao , Yan Wang , Manman Liu , Jing Xu , Xingli Zhang , Tao Yu , Shucheng Gan , Dongfang Dai , Xuan Luo , Qingyan Lu , Chaoming Mao , Yanyun Zhang , Nan Shen , Bin Li , Mingzhu Huang , Xiaodong Zhu , Jin Jin , Xuhong Cheng , Shao-Cong Sun , Yichuan Xiao

Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-κB signaling. Mechanically, Peli1 functions as an E3 ligase to associate with NF-κB inducing kinase (NIK) and mediates NIK Lys48 ubiquitination and degradation. Overexpression of Peli1 inhibits noncanonical NF-κB activation and alleviates lupus-like disease. In humans, PELI1 levels negatively correlate with disease severity in SLE patients. Our findings establish Peli1 as a negative regulator of the noncanonical NF-κB pathway in the context of restraining the pathogenesis of lupus-like disease.

中文翻译:

Peli1负调节非规范性NF-κB信号传导,以抑制系统性红斑狼疮。

系统性红斑狼疮(SLE)的特征在于浆细胞分泌的自身抗体不受控制。尽管血浆细胞和自身抗体在SLE中的功能重要性已得到充分确立,但控制自身抗体产生的潜在分子机制仍知之甚少。在这里,我们显示Peli1具有B细胞内在功能,可预防小鼠中的狼疮样自身免疫。B细胞中Peli1缺乏症通过非规范的NF-κB信号传导诱导自身抗体的产生。在机械上,Peli1充当E3连接酶,与NF-κB诱导激酶(NIK)结合并介导NIK Lys48泛素化和降解。Peli1的过表达抑制非规范性NF-κB活化并减轻狼疮样疾病。在人类中,SLE患者中PELI1水平与疾病严重程度负相关。
更新日期:2018-03-19
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