| Autor: |
Correa-Medero, Luis O., Jankowski, Shayna E., Hong, Hanna S., Armas, Nicholas D., Vijendra, Aditi I., Reynolds, Mack B., Fogo, Garrett M., Awad, Dominik, Dils, Alexander T., Inoki, Kantaro A., Williams, Reid G., Ye, Annabelle M., Svezhova, Nadezhda, Gomez-Rivera, Francisco, Collins, Kathleen L., O’Riordan, Mary X., Sanderson, Thomas H., Lyssiotis, Costas A., Carty, Shannon A. |
| Zdroj: |
Cell Reports; May 2024, Vol. 43 Issue: 5 |
| Abstrakt: |
The maintenance of antigen-specific CD8+T cells underlies the efficacy of vaccines and immunotherapies. Pathways contributing to CD8+T cell loss are not completely understood. Uncovering the pathways underlying the limited persistence of CD8+T cells would be of significant benefit for developing novel strategies of promoting T cell persistence. Here, we demonstrate that murine CD8+T cells experience endoplasmic reticulum (ER) stress following activation and that the ER-associated degradation (ERAD) adapter Sel1L is induced in activated CD8+T cells. Sel1L loss limits CD8+T cell function and memory formation following acute viral infection. Mechanistically, Sel1L is required for optimal bioenergetics and c-Myc expression. Finally, we demonstrate that human CD8+T cells experience ER stress upon activation and that ER stress is negatively associated with improved T cell functionality in T cell-redirecting therapies. Together, these results demonstrate that ER stress and ERAD are important regulators of T cell function and persistence. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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