Tissue adaptation of regulatory T cells in adipose tissue

Foxp3⁺ regulatory T (Treg) cells critically suppress over-activated immune responses and therefore maintain immune homeostasis. Adipose tissue-resident Treg (AT Treg) cells are known for modulating immunity and metabolism in adipose tissue microenvironment through various physiological signals, as well as their heterogeneous subsets, which potentially play disparate roles in aging and obesity. Recent single-cell studies of Treg cells have revealed specialized trajectories of their tissue adaptation and development in lymphoid tissues and at barrier sites. Here, we reviewed a T Cell Receptor (TCR)-primed environmental cue-boosted model of adipose Treg cells' tissue adaptation, especially in response to IL-33, IFN-α, insulin, and androgen signals, which trigger sophisticated transcriptional cascades and ultimately establish unique transcriptional modules in adipose Treg cell subsets. In addition, we further discuss potential therapeutic strategies against aging and obesity by blocking detrimental environmental cues, strengthening the functions of specific AT Treg subsets and modifying the communications between AT Treg subsets and adipocytes.