| First Author | Naik E | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 10 | Pages | 1947-55 |
| PubMed ID | 25200027 | Mgi Jnum | J:218690 |
| Mgi Id | MGI:5618200 | Doi | 10.1084/jem.20140860 |
| Citation | Naik E, et al. (2014) Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X. J Exp Med 211(10):1947-55 |
| abstractText | The T cell hyperproliferation and autoimmune phenotypes that manifest in mice lacking E3 ubiquitin ligases such as Cbl, ITCH, or GRAIL highlight the importance of ubiquitination for the maintenance of peripheral T cell tolerance. Less is known, however, about the deubiquitinating enzymes that regulate T cell proliferation and effector function. Here, we define a cell intrinsic role for the deubiquitinase Usp9X during proximal TCR signaling. Usp9X-deficient T cells were hypoproliferative, yet mice with T cell-specific Usp9x deletion had elevated numbers of antigen-experienced T cells and expanded PD-1 and OX40-expressing populations consistent with immune hyperactivity. Aged Usp9x KO mice developed lupus-like autoimmunity and lymphoproliferative disease, indicating that ubiquitin ligases and deubiquitinases maintain the delicate balance between effective immunity and self-tolerance. |
