Single T-cell landscape identifies tissue regeneration program in murine and human regulatory T cells

Several studies over the past decade identified a subpopulation of murine regulatory T cells (Tregs) which have the intrinsic capacity to promote tissue homeostasis and, upon damage, enhance tissue regeneration and re-organization. In humans, this population of tissue regeneration-promoting Treg cells has not been identified and characterized yet. Using single-cell chromatin accessibility as well as single-cell RNA and TCR expression profiles of murine and human tissue-derived CD4 T cells, we identified the murine Treg repair signature and performed a liftover on human single T cell data. We identified a FOXP3+CCR8+HLA-DR+ population in peripheral blood, which has characteristics of human tissue Treg cells and promotes tissue regeneration and wound healing in-vitro. This population was dependent on the transcriptional regulator BATF, a factor that also drives the development of tissue regeneration-promoting Treg cells in the murine system. Human CCR8+HLA-DR+ Treg cells could be used as a novel T-cell product to promote tissue repair in regenerative medicine.