| First Author | Chyuan IT | Year | 2022 |
| Journal | J Immunol | Volume | 208 |
| Issue | 7 | Pages | 1534-1544 |
| PubMed ID | 35264458 | Mgi Jnum | J:324698 |
| Mgi Id | MGI:7281016 | Doi | 10.4049/jimmunol.2100788 |
| Citation | Chyuan IT, et al. (2022) T Cell-Specific Deletion of TRAIL Receptor Reveals Its Critical Role for Regulating Pathologic T Cell Activation and Disease Induction in Experimental Autoimmune Encephalomyelitis. J Immunol 208(7):1534-1544 |
| abstractText | Recent evidence from several autoimmune animal models has demonstrated that TRAIL suppresses the activation of T cells and inhibits autoimmune inflammation via an apoptosis-independent pathway. However, it remains unclear whether the immunosuppressive effects of TRAIL are dependent on its direct effects on T cells or on other immune cells to regulate T cells for the induction of disease. Therefore, we generated mice with T cell-specific TRAIL receptor (TRAIL-R) conditional knockout to investigate the impact of TRAIL on autoimmune inflammation and disease induction in experimental autoimmune encephalomyelitis (EAE). T cell-specific TRAIL-R knockout mice were found to completely reverse the TRAIL-mediated suppression of inflammation and disease induction, indicating that TRAIL-R on T cells is essential for TRAIL-mediated suppression of inflammation and disease induction in EAE. Moreover, the immune suppression effects were not due to the induction of cell apoptosis, but to the direct inhibition of T cell activation. In addition, RNA sequencing and transcriptome analysis revealed that TRAIL-R signaling significantly downregulated the genes involved in TCR signaling pathways, T cell differentiation, and proinflammatory cytokines. These results indicate that TRAIL-R on T cells is critical for pathologic T cell activation and induction of inflammation in EAE, suggesting that TRAIL-R serves as a novel immune checkpoint receptor in T cell-mediated autoimmune diseases. |
