| First Author | Rome KS | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 5 | PubMed ID | 32150623 |
| Mgi Jnum | J:289862 | Mgi Id | MGI:6432500 |
| Doi | 10.1084/jem.20190888 | Citation | Rome KS, et al. (2020) Trib1 regulates T cell differentiation during chronic infection by restraining the effector program. J Exp Med 217(5) |
| abstractText | In chronic infections, the immune response fails to control virus, leading to persistent antigen stimulation and the progressive development of T cell exhaustion. T cell effector differentiation is poorly understood in the context of exhaustion, but targeting effector programs may provide new strategies for reinvigorating T cell function. We identified Tribbles pseudokinase 1 (Trib1) as a central regulator of antiviral T cell immunity, where loss of Trib1 led to a sustained enrichment of effector-like KLRG1+ T cells, enhanced function, and improved viral control. Single-cell profiling revealed that Trib1 restrains a population of KLRG1+ effector CD8 T cells that is transcriptionally distinct from exhausted cells. Mechanistically, we identified an interaction between Trib1 and the T cell receptor (TCR) signaling activator, MALT1, which disrupted MALT1 signaling complexes. These data identify Trib1 as a negative regulator of TCR signaling and downstream function, and reveal a link between Trib1 and effector versus exhausted T cell differentiation that can be targeted to improve antiviral immunity. |
