Kälin, StefanieBecker, MaikeOtt, Verena B.Serr, IsabelleHosp, FabianMollah, Mohammad M.H.Keipert, SusanneLamp, DanielRohner-Jeanrenaud, FrancoiseFlynn, Victoria K.Scherm, Martin G.Nascimento, Lucas F.R.Gerlach, KatharinaPopp, VanessaDietzen, SarahBopp, TobiasKrishnamurthy, PurnaKaplan, Mark H.Serrano, ManuelWoods, Stephen C.Tripal, PhilippPalmisano, RalfJastroch, MartinBlüher, MatthiasWolfrum, ChristianWeigmann, BennoZiegler, Anette-GabrieleMann, MatthiasTschöp, Matthias H.Daniel, Carolin2019-04-302019-04-302017-09-05Kälin, S., Becker, M., Ott, V. B., Serr, I., Hosp, F., Mollah, M., … Daniel, C. (2017). A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function. Cell metabolism, 26(3), 475–492.e7. doi:10.1016/j.cmet.2017.08.008https://hdl.handle.net/1805/19014Obesity and type 2 diabetes are associated with metabolic defects and adipose tissue inflammation. Foxp3+ regulatory T cells (Tregs) control tissue homeostasis by counteracting local inflammation. However, if and how T cells interlink environmental influences with adipocyte function remains unknown. Here, we report that enhancing sympathetic tone by cold exposure, beta3-adrenergic receptor (ADRB3) stimulation or a short-term high-calorie diet enhances Treg induction in vitro and in vivo. CD4+ T cell proteomes revealed higher expression of Foxp3 regulatory networks in response to cold or ADRB3 stimulation in vivo reflecting Treg induction. Specifically, Ragulator-interacting protein C17orf59, which limits mTORC1 activity, was upregulated in CD4+ T cells by either ADRB3 stimulation or cold exposure, suggesting contribution to 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 offer a new mechanistic model in which tissue-specific Tregs maintain adipose tissue function.en-USPublisher PolicyBorcs6C17orf59Foxp3PTENSTAT6T cellsTregsAdipose tissue functionCold exposureMetabolic functionMetabolismRegulatory T cellsArticle