Maintenance DNA methylation is necessary for age-related alterations in regulatory T cell transcriptional and DNA methylation signatures
Gurkan, J. K.; Liu, Q.; Reyes Flores, C. P.; Helmin, K. A.; Ryan, D. H.; Joudi, A. M.; Ulrich, B. J.; Abdala-Valencia, H.; Steinert, E. M.; Singer, B. D.
Show abstract
CD4+FOXP3+ 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.
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