| First Author | Zhu C | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 18 | PubMed ID | 33931442 |
| Mgi Jnum | J:338689 | Mgi Id | MGI:6811522 |
| Doi | 10.1126/sciadv.abd2710 | Citation | Zhu C, et al. (2021) Tim-3 adaptor protein Bat3 is a molecular checkpoint of T cell terminal differentiation and exhaustion. Sci Adv 7(18) |
| abstractText | T cell exhaustion has been associated with poor prognosis in persistent viral infection and cancer. Conversely, in the context of autoimmunity, T cell exhaustion has been favorably correlated with long-term clinical outcome. Understanding the development of exhaustion in autoimmune settings may provide underlying principles that can be exploited to quell autoreactive T cells. Here, we demonstrate that the adaptor molecule Bat3 acts as a molecular checkpoint of T cell exhaustion, with deficiency of Bat3 promoting a profound exhaustion phenotype, suppressing autoreactive T cell-mediated neuroinflammation. Mechanistically, Bat3 acts as a critical mTORC2 inhibitor to suppress Akt function. As a result, Bat3 deficiency leads to increased Akt activity and FoxO1 phosphorylation, indirectly promoting Prdm1 expression. Transcriptional analysis of Bat3 (-/-) T cells revealed up-regulation of dysfunction-associated genes, concomitant with down-regulation of genes associated with T cell effector function, suggesting that absence of Bat3 can trigger T cell dysfunction even under highly proinflammatory autoimmune conditions. |
