| First Author | Adoro S | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 7 | Pages | 780-790 |
| PubMed ID | 28553951 | Mgi Jnum | J:258169 |
| Mgi Id | MGI:6140972 | Doi | 10.1038/ni.3764 |
| Citation | Adoro S, et al. (2017) Post-translational control of T cell development by the ESCRT protein CHMP5. Nat Immunol 18(7):780-790 |
| abstractText | The acquisition of a protective vertebrate immune system hinges on the efficient generation of a diverse but self-tolerant repertoire of T cells by the thymus through mechanisms that remain incompletely resolved. Here we identified the endosomal-sorting-complex-required-for-transport (ESCRT) protein CHMP5, known to be required for the formation of multivesicular bodies, as a key sensor of thresholds for signaling via the T cell antigen receptor (TCR) that was essential for T cell development. CHMP5 enabled positive selection by promoting post-selection thymocyte survival in part through stabilization of the pro-survival protein Bcl-2. Accordingly, loss of CHMP5 in thymocyte precursor cells abolished T cell development, a phenotype that was ''rescued'' by genetic deletion of the pro-apoptotic protein Bim or transgenic expression of Bcl-2. Mechanistically, positive selection resulted in the stabilization of CHMP5 by inducing its interaction with the deubiquitinase USP8. Our results thus identify CHMP5 as an essential component of the post-translational machinery required for T cell development. |
