FOXO1 constrains activation and regulates senescence in CD8 T cells
| Autor: | Stephen M. Hedrick, Liyen Loh, Karmel A. Allison, Christopher K. Glass, Arnaud Delpoux, Andrew L. Doedens, Rodrigo Hess Michelini, Katherine Kedzierska, Sergio M. Quiñones-Parra, Carol D. Katayama, Cornelis Murre, Martha Lappas, Nimi Marcel |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
0301 basic medicine Senescence FOXO1 CD8-Positive T-Lymphocytes Biology General Biochemistry Genetics and Molecular Biology Mice Young Adult 03 medical and health sciences 0302 clinical medicine Antigen Animals Humans Cytotoxic T cell Protein kinase A Cellular Senescence Aged Aged 80 and over Forkhead Box Protein O1 Effector c-jun Middle Aged Cell biology Mice Inbred C57BL 030104 developmental biology 030217 neurology & neurosurgery CD8 |
| Zdroj: | Cell Reports. 34:108674 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2020.108674 |
| Popis: | Naive and memory T cells are maintained in a quiescent state, yet capable of rapid response and differentiation to antigen challenge via molecular mechanisms that are not fully understood. In naive cells, the deletion of Foxo1 following thymic development results in the increased expression of multiple AP-1 family members, rendering T cells less able to respond to antigenic challenge. Similarly, in the absence of FOXO1, post-infection memory T cells exhibit the characteristics of extended activation and senescence. Age-based analysis of human peripheral T cells reveals that levels of FOXO1 and its downstream target, TCF7, are inversely related to host age, whereas the opposite is found for AP-1 factors. These characteristics of aging also correlate with the formation of T cells manifesting features of cellular senescence. Our work illustrates a role for FOXO1 in the active maintenance of stem-like properties in T cells at the timescales of acute infection and organismal life span. |
| Databáze: | OpenAIRE |
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