| First Author | Chang M | Year | 2011 |
| Journal | Nat Immunol | Volume | 12 |
| Issue | 10 | Pages | 1002-9 |
| PubMed ID | 21874024 | Mgi Jnum | J:176455 |
| Mgi Id | MGI:5291872 | Doi | 10.1038/ni.2090 |
| Citation | Chang M, et al. (2011) The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity. Nat Immunol 12(10):1002-9 |
| abstractText | 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-beta (TGF-beta). 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-kappaB 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. |
