Summary Obesity and type-2 diabetes are associated with tissue-inflammation and metabolic defects in fat depots. Foxp3+regulatory T(Treg) cells mediate T-cell tolerance, thereby controlling tissue inflammation. However, the molecular underpinnings how environmental stimuli interlink T-cell tolerance with adipose tissue function remain largely unknown. Here, we report that cold exposure or beta3-adrenergic receptor (ADRB3) stimulation induces T-cell tolerance in vitro and in murine and humanized models. Tolerance induction was verified by CD4+T-cell-proteomes revealing higher protein expression of Foxp3 regulatory networks. Specifically, Ragulator-interacting protein C17orf59, which limits mTORC1 activity, was upregulated by either ADRB3-stimulation or cold-exposure, and therefore might enhance Treg induction. By loss and gain-of-function studies, including Treg depletion and transfers in vivo, we demonstrated that a T-cell-specific Stat6/Pten axis links cold-exposure or ADRB3 stimulation with Foxp3+Treg induction and adipose tissue function. Our findings open new avenues in understanding tissue-specific T-cell tolerance and the design of precision concepts toward personalized immune-metabolic health.