| Autor: |
Lina Sun, Anjun Jiao, Haiyan Liu, Renyi Ding, Ning Yuan, Biao Yang, Cangang Zhang, Xiaoxuan Jia, Gang Wang, Yanhong Su, Dan Zhang, Lin Shi, Chenming Sun, Aijun Zhang, Lianjun Zhang, Baojun Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Signal Transduction and Targeted Therapy, Vol 9, Iss 1, Pp 1-15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2059-3635 |
| DOI: |
10.1038/s41392-024-01873-6 |
| Popis: |
Abstract CD8+ T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8+ T cells. Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8+ T cells. T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8+ T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8+ T cells through cleavage of membrane CD122. ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8+ T cells. Intriguingly, inhibition of ADAM17 in CD8+ T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumors. Our findings reveal a critical post-translational regulation in CD8+ T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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