FOXO1 deficiency impairs proteostasis in aged T cells.

ABSTRACT: T cell differentiation involves the dynamic regulation of FOXO1 expression, which rapidly declines after activation and is subsequently restored. Reexpression is impaired in naïve CD4⁺ T cell responses from older individuals. Here, we show that FOXO1 promotes lysosome function through the induction of the key transcription factor for lysosomal proteins, TFEB. Subdued FOXO1 reexpression in activated CD4⁺ T cells impairs lysosomal activity, causing an expansion of multivesicular bodies (MVBs). Expansion of the MVB compartment induces the sequestration of glycogen synthase kinase 3β (GSK3β), thereby suppressing protein turnover and enhancing glycolytic activity. As a consequence, older activated CD4⁺ T cells develop features reminiscent of senescent cells. The

SUBMITTER: Jin J 

PROVIDER: S-EPMC7176426 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature