{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jeng MY"],"funding":["NIDA NIH HHS","NCRR NIH HHS","NIAID NIH HHS"],"pagination":["51-62"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5748845"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["215(1)"],"pubmed_abstract":["The expansion of CD8+CD28- T cells, a population of terminally differentiated memory T cells, is one of the most consistent immunological changes in humans during aging. CD8+CD28- T cells are highly cytotoxic, and their frequency is linked to many age-related diseases. As they do not accumulate in mice, many of the molecular mechanisms regulating their fate and function remain unclear. In this paper, we find that human CD8+CD28- T cells, under resting conditions, have an enhanced capacity to use glycolysis, a function linked to decreased expression of the NAD+-dependent protein deacetylase SIRT1. Global gene expression profiling identified the transcription factor FoxO1 as a SIRT1 target involved in transcriptional reprogramming of CD8+CD28- T cells. FoxO1 is proteasomally degraded in SIRT1-deficient CD8+CD28- T cells, and inhibiting its activity in resting CD8+CD28+ T cells enhanced glycolytic capacity and granzyme B production as in CD8+CD28- T cells. These data identify the evolutionarily conserved SIRT1-FoxO1 axis as a regulator of resting CD8+ memory T cell metabolism and activity in humans."],"journal":["The Journal of experimental medicine"],"pubmed_title":["Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1."],"pmcid":["PMC5748845"],"funding_grant_id":["P30 AI027763","DP1 DA038043","S10 RR028962"],"pubmed_authors":["Johnson J","Kwon HS","Ott M","Kasler H","Krogan N","Jeng MY","Fei M","Tsou CL","Ng CP","Gordon DE","Verdin E","Hull PA"],"additional_accession":[]},"is_claimable":false,"name":"Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1.","description":"The expansion of CD8+CD28- T cells, a population of terminally differentiated memory T cells, is one of the most consistent immunological changes in humans during aging. CD8+CD28- T cells are highly cytotoxic, and their frequency is linked to many age-related diseases. As they do not accumulate in mice, many of the molecular mechanisms regulating their fate and function remain unclear. In this paper, we find that human CD8+CD28- T cells, under resting conditions, have an enhanced capacity to use glycolysis, a function linked to decreased expression of the NAD+-dependent protein deacetylase SIRT1. Global gene expression profiling identified the transcription factor FoxO1 as a SIRT1 target involved in transcriptional reprogramming of CD8+CD28- T cells. FoxO1 is proteasomally degraded in SIRT1-deficient CD8+CD28- T cells, and inhibiting its activity in resting CD8+CD28+ T cells enhanced glycolytic capacity and granzyme B production as in CD8+CD28- T cells. These data identify the evolutionarily conserved SIRT1-FoxO1 axis as a regulator of resting CD8+ memory T cell metabolism and activity in humans.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Jan","modification":"2020-11-09T08:53:59Z","creation":"2019-03-26T23:44:08Z"},"accession":"S-EPMC5748845","cross_references":{"pubmed":["29191913"],"doi":["10.1084/jem.20161066"]}}