Maintenance DNA methylation is necessary for age-related alterations in regulatory T cell transcriptional and DNA methylation signatures
Year: 2026
Type: preprint
Abstract: regulatory T (Treg) cells maintain self-tolerance, restrain immune responses during inflammatory stimuli, and promote tissue function and repair. Treg cell lineage identity, stability, and function depend on specific DNA methylation patterns maintained by the epigenetic regulator, UHRF1. Aging disrupts DNA methylation patterns necessary for Treg cell-mediated lung repair in a cell-autonomous manner. Nevertheless, whether maintenance DNA methylation is necessary for age-related Treg cell transcriptional and methylation programs is unknown. Here, we performed transcriptional and DNA methylation profiling on young and old Treg cells isolated from mice with chimeric Treg cell-specific loss of UHRF1. We observed cell-autonomous, age-related alterations in transcriptional and DNA methylation signatures that were dependent on UHRF1. We conclude that maintenance DNA methylation is required for age-related alterations in Treg cell transcriptional and DNA methylation signatures.
Institution: Northwestern University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Epigenetic modifiers of regulatory T cell function following viral pneumonia, FACSAria SORP Cell Sorter, Disordered Proteostasis as a Driver of Disease in the Aging Lung, The role of epigenetic regulator UHRF1 in stability of induced regulatory T-cell function during influenza A virus-induced lung injury, Mechanisms of regulatory T cell-mediated recovery from severe viral pneumonia, Metabolic regulation of regulatory T cells through fatty acid metabolism during viral pneumonia, Midwest Murine-Tissue Mapping Center (MM-TMC), The Robert H. Lurie Comprehensive Cancer Center, Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center, Medical Scientist Training Program, The Neu-Lung Consortium: Neutrophilic Mechanisms of Inflammation, Injury, and Repair in Lung and Airways Diseases, Mechanisms of Recovery from Viral Pneumonia, Training Program in Lung Sciences
OpenAlex ID: W7166588039