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Publication : FOXO1 constrains activation and regulates senescence in CD8 T cells.

First Author  Delpoux A Year  2021
Journal  Cell Rep Volume  34
Issue  4 Pages  108674
PubMed ID  33503413 Mgi Jnum  J:312323
Mgi Id  MGI:6716755 Doi  10.1016/j.celrep.2020.108674
Citation  Delpoux A, et al. (2021) FOXO1 constrains activation and regulates senescence in CD8 T cells. Cell Rep 34(4):108674
abstractText  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.
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