https://scholars.lib.ntu.edu.tw/handle/123456789/641471
標題: | T Cell-Specific Deletion of TRAIL Receptor Reveals Its Critical Role for Regulating Pathologic T Cell Activation and Disease Induction in Experimental Autoimmune Encephalomyelitis | 作者: | Chyuan, I-Tsu CHING-LIANG CHU Hsu, Chia-Lang Pan, Meng-Hsun Liao, Hsiu-Jung Wu, Chien-Sheng PING-NING HSU |
公開日期: | 1-四月-2022 | 出版社: | American Association of Immunologists | 卷: | 208 | 期: | 7 | 起(迄)頁: | 1534 - 1544 | 來源出版物: | Journal of Immunology | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/641471 | ISSN: | 00221767 | DOI: | 10.4049/jimmunol.2100788 |
顯示於: | 免疫學研究所 |
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