Journal article
Developmental epigenetic programming by Tet1/3 determines peripheral CD8 T cell fate
EMBO reports, Vol.26(10), pp.2494-2518
05/27/2025
DOI: 10.1038/s44319-025-00439-z
PMCID: PMC12116802
PMID: 40175595
Abstract
In response to infections, naive CD8 T cells give rise to effector and memory T cells. However, eliciting long-lived memory CD8 T cells remains a challenge for many infections. DNA demethylation of cytosines within CpG dinucleotides by Tet enzymes is a key epigenetic mechanism that regulates short- and long-term transcriptional programs in cells. Currently, their roles in modulating CD8 T-cell effector and memory differentiation are unclear. Here, we report that developing CD8 T cells lacking Tet1/3 preferentially differentiate into short-lived effector and effector memory cells following acute infection. Using genome-wide analyses, mice in which Tet1/3 were ablated during T-cell development and mature CD8 T cells, respectively, we show that Tet1/3 regulates these cell fates by licensing the chromatin landscape of genes downstream of T-cell receptor activation during thymic T-cell maturation. However, in mature CD8 T cells, Tet1/3 are dispensable for effector and memory cell fates. These findings unveil context-specific roles of DNA demethylation, which are essential for defining pathways that contribute to CD8 memory T-cell generation in response to infections.
Details
- Title: Subtitle
- Developmental epigenetic programming by Tet1/3 determines peripheral CD8 T cell fate
- Creators
- Kara M Misel-Wuchter - Department of Internal Medicine, University of Iowa, Iowa City, IA, USAAndrew L Thurman - University of IowaJordan T Johnson - Immunology Graduate Program, University of Iowa, Iowa City, IA, USAAthmane Teghanemt - University of IowaNeelam Gautam - University of IowaAlejandro A Pezzulo - Department of Internal Medicine, University of Iowa, Iowa City, IA, USAJennifer R Bermick - University of IowaNoah S Butler - University of IowaPriya D Issuree - Immunology Graduate Program, University of Iowa, Iowa City, IA, USA. priya-issuree@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- EMBO reports, Vol.26(10), pp.2494-2518
- DOI
- 10.1038/s44319-025-00439-z
- PMID
- 40175595
- PMCID
- PMC12116802
- NLM abbreviation
- EMBO Rep
- ISSN
- 1469-3178
- eISSN
- 1469-3178
- Publisher
- SPRINGERNATURE
- Grant note
- 1R01HL163024 / HHS | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) 1R35GM154831-01 / HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01163058 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01127481 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) F31A1164640 / HHS | NIH | NIAID | Division of Intramural Research (DIR, NIAID) R01125446 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32AI007511 / HHS | NIH | NIAID | Division of Intramural Research (DIR, NIAID)
- Language
- English
- Electronic publication date
- 04/02/2025
- Date published
- 05/27/2025
- Academic Unit
- Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Infectious Diseases; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neonatology; Internal Medicine
- Record Identifier
- 9984803712902771
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