description |
Regulatory T cells (Treg) perform two distinct functions: they maintain self-tolerance and support organ homeostasis by differentiation into specialized tissue Treg cells. We now report that epigenetic adaptations define molecular characteristics of tissue Treg cells. Whole-genome bisulfite sequencing of tissue and lymphoid T cells revealed more than 11,000 differential methylated regions (DMRs) associated with about 4000 genes. Only 339 of those DMRs separated lymph node Treg from conventional T cells. In contrast, about 1,600 DMRs distinguished individual tissue from lymph node Treg cells, translating into discrete gene and protein expression signatures. These findings led to the identification of a type-2 tissue Treg population, present in many organs, and characterized by gain and loss of methylation at specific sites including Gata3, Irf4, Batf, Maf, Rora, Il33r and Il10. Thus, the epigenetic landscape helps to define Treg cell identities and molecular programs. |