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- Title
The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity.
- Authors
Chang, Mikyoung; Jin, Wei; Chang, Jae-Hoon; Xiao, Yichuan; Brittain, George C; Yu, Jiayi; Zhou, Xiaofei; Wang, Yi-Hong; Cheng, Xuhong; Li, Pingwei; Rabinovich, Brian A; Hwu, Patrick; Sun, Shao-Cong
- Abstract
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.
- Publication
Nature immunology, 2011, Vol 12, Issue 10, p1002
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.2090