| First Author | Li Y | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 9 | Pages | 1175-1185 |
| PubMed ID | 34429546 | Mgi Jnum | J:326972 |
| Mgi Id | MGI:6874459 | Doi | 10.1038/s41590-021-01010-3 |
| Citation | Li Y, et al. (2021) Insulin signaling establishes a developmental trajectory of adipose regulatory T cells. Nat Immunol 22(9):1175-1185 |
| abstractText | Systematic characterizations of adipose regulatory T (Treg) cell subsets and their phenotypes remain uncommon. Using single-cell ATAC-sequencing and paired single-cell RNA and T cell receptor (TCR) sequencing to map mouse adipose Treg cells, we identified CD73(hi)ST2(lo) and CD73(lo)ST2(hi) subsets with distinct clonal expansion patterns. Analysis of TCR-sharing data implied a state transition between CD73(hi)ST2(lo) and CD73(lo)ST2(hi) subsets. Mechanistically, we revealed that insulin signaling occurs through a HIF-1alpha-Med23-PPAR-gamma axis to drive the transition of CD73(hi)ST2(lo) into a CD73(lo)ST2(hi) adipose Treg cell subset. Treg cells deficient in insulin receptor, HIF-1alpha or Med23 have decreased PPAR-gamma expression that in turn promotes accumulation of CD73(hi)ST2(lo) adipose Treg cells and physiological adenosine production to activate beige fat biogenesis. We therefore unveiled a developmental trajectory of adipose Treg cells and its dependence on insulin signaling. Our findings have implications for understanding the dynamics of adipose Treg cell subsets in aged and obese contexts. |
