| First Author | Dufner A | Year | 2015 |
| Journal | Nat Immunol | Volume | 16 |
| Issue | 9 | Pages | 950-60 |
| PubMed ID | 26214742 | Mgi Jnum | J:233111 |
| Mgi Id | MGI:5780791 | Doi | 10.1038/ni.3230 |
| Citation | Dufner A, et al. (2015) The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells. Nat Immunol 16(9):950-60 |
| abstractText | The modification of proteins by ubiquitin has a major role in cells of the immune system and is counteracted by various deubiquitinating enzymes (DUBs) with poorly defined functions. Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3beta. Caspase-dependent processing of USP8 occurred after stimulation of the TCR. T cell-specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte maturation and upregulation of the gene encoding the cytokine receptor IL-7Ralpha mediated by the transcription factor Foxo1. Mice with T cell-specific USP8 deficiency developed colitis that was promoted by disturbed T cell homeostasis, a predominance of CD8(+) gammadelta T cells in the intestine and impaired regulatory T cell function. Collectively, our data reveal an unexpected role for USP8 as an immunomodulatory DUB in T cells. |
