Journal article

FOXO1 constrains activation and regulates senescence in CD8 T cells

Arnaud Delpoux, Nimi Marcel, Rodrigo Hess Michelini, Carol D Katayama, Karmel A Allison, Christopher K Glass, Sergio M Quinones-Parra, Cornelis Murre, Liyen Loh, Katherine Kedzierska, Martha Lappas, Stephen M Hedrick, Andrew L Doedens

CELL REPORTS | CELL PRESS | Published : 2021

Abstract

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 A..

View full abstract

Grants

Awarded by National Institutes of Health (U.S.A.)


Funding Acknowledgements

This work was supported by the National Institutes of Health (U.S.A.) grants R01AI073885 and R01AI103440 to S.M.H. We thank Ming Li (Memorial Sloan Kettering) for providing the Foxo1-AAA mice. Allen Yaldiko carried out genotyping, assisted in the maintenance of animal colonies, and contributed to essential biochemical experiments. This work is published in memory of A.D., who passed away during the preparation of this manuscript.