作者
Mikyoung Chang, Wei Jin, Jae-Hoon Chang, Yichuan Xiao, George C Brittain, Jiayi Yu, Xiaofei Zhou, Yi-Hong Wang, Xuhong Cheng, Pingwei Li, Brian A Rabinovich, Patrick Hwu, Shao-Cong Sun
发表日期
2011/10
期刊
Nature immunology
卷号
12
期号
10
页码范围
1002-1009
出版商
Nature Publishing Group US
简介
T cell activation is subject to tight regulation to avoid inappropriate responses to self antigens. Here we show that genetic deficiency in the ubiquitin ligase Peli1 caused hyperactivation of T cells and rendered T cells refractory to suppression by regulatory T cells and transforming growth factor-β (TGF-β). As a result, Peli1-deficient mice spontaneously developed autoimmunity characterized by multiorgan inflammation and autoantibody production. Peli1 deficiency resulted in the nuclear accumulation of c-Rel, a member of the NF-κB family of transcription factors with pivotal roles in T cell activation. Peli1 negatively regulated c-Rel by mediating its Lys48 (K48) ubiquitination. Our results identify Peli1 as a critical factor in the maintenance of peripheral T cell tolerance and demonstrate a previously unknown mechanism of c-Rel regulation.
学术搜索中的文章
M Chang, W Jin, JH Chang, Y Xiao, GC Brittain, J Yu… - Nature immunology, 2011