A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function.

Kälin, Stefanie; Becker, Maike; Ott, Verena B; Serr, Isabelle; Hosp, Fabian; Mollah, Mohammad M H; Keipert, Susanne; Lamp, Daniel; Rohner-Jeanrenaud, Francoise; Flynn, Victoria K; Scherm, Martin G; Nascimento, Lucas F R; Gerlach, Katharina; Popp, Vanessa; Dietzen, Sarah; Bopp, Tobias; Krishnamurthy, Purna; Kaplan, Mark H; Serrano, Manuel; Woods, Stephen C; Tripal, Philipp; Palmisano, Ralf; Jastroch, Martin; Blüher, Matthias; Wolfrum, Christian; Weigmann, Benno; Ziegler, Anette-Gabriele; Mann, Matthias; Tschöp, Matthias H; Daniel, Carolin     «

Kälin, Stefanie; Becker, Maike; Ott, Verena B; Serr, Isabelle; Hosp, Fabian; Mollah, Mohammad M H; Keipert, Susanne; Lamp, Daniel; Rohner-Jeanrenaud, Francoise; Flynn, Victoria K; Scherm, Martin G; Nascimento, Lucas F R; Gerlach, Katharina; Popp, Vanessa; Dietzen, Sarah; Bopp, Tobias; Krishnamurthy, Purna; Kaplan, Mark H; Serrano, Manuel; Woods, Stephen C; Tripal, Philipp; Palmisano, Ralf; Jastroch, Martin; Blüher, Matthias; Wolfrum, Christian; Weigmann, Benno; Ziegler, Anette-Gabriele; Mann, Ma...     »

Obesity 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.      «

Obesity 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...     »