| First Author | Yu J | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6074 | PubMed ID | 25606824 |
| Mgi Jnum | J:219715 | Mgi Id | MGI:5629612 |
| Doi | 10.1038/ncomms7074 | Citation | Yu J, et al. (2015) Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation. Nat Commun 6:6074 |
| abstractText | Development of an immune or autoimmune response involves T-cell activation in lymphoid organs and subsequent migration to peripheral tissues. Here we show that T-cell-specific ablation of the kinase TBK1 promotes T-cell activation but causes retention of effector T cells in the draining lymph node in a neuroinflammatory autoimmunity model, experimental autoimmune encephalomyelitis (EAE). At older ages, the T-cell-conditional TBK1-knockout mice also spontaneously accumulate T cells with activated phenotype. TBK1 controls the activation of AKT and its downstream kinase mTORC1 by a mechanism involving TBK1-stimulated AKT ubiquitination and degradation. The deregulated AKT-mTORC1 signalling in turn contributes to enhanced T-cell activation and impaired effector T-cell egress from draining lymph nodes. Treatment of mice with a small-molecule inhibitor of TBK1 inhibits EAE induction. These results suggest a role for TBK1 in regulating T-cell migration and establish TBK1 as a regulator of the AKT-mTORC1 signalling axis. |
