Peli1 negatively regulates T-cell activation and prevents autoimmunity
| Autor: | Yichuan Xiao, Pingwei Li, Patrick Hwu, Xuhong Cheng, Shao Cong Sun, Wei Jin, Jae Hoon Chang, Jiayi Yu, Brian Rabinovich, Mikyoung Chang, Yi Hong Wang, George C. Brittain, Xiaofei Zhou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
T cell
T-Lymphocytes Ubiquitin-Protein Ligases Immunology Receptors Antigen T-Cell Autoimmunity Lymphocyte Activation T-Lymphocytes Regulatory Article 03 medical and health sciences Mice 0302 clinical medicine Ubiquitin CD28 Antigens Transforming Growth Factor beta medicine Immunology and Allergy Animals Nuclear protein Transcription factor 030304 developmental biology 0303 health sciences biology NF-kappa B Ubiquitination Nuclear Proteins Transforming growth factor beta NFKB1 Proto-Oncogene Proteins c-rel Ubiquitin ligase Mice Inbred C57BL medicine.anatomical_structure biology.protein Cancer research 030215 immunology Transforming growth factor |
| Zdroj: | Nature immunology |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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