5 years ago

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

A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function
Daniel Lamp, Isabelle Serr, Benno Weigmann, Francoise Rohner-Jeanrenaud, Matthias Blüher, Martin Jastroch, Anette-Gabriele Ziegler, Philipp Tripal, Tobias Bopp, Vanessa Popp, Carolin Daniel, Matthias H. Tschöp, Manuel Serrano, Purna Krishnamurthy, Christian Wolfrum, Martin G. Scherm, Maike Becker, Mark H. Kaplan, Victoria K. Flynn, Susanne Keipert, Mohammad M.H. Mollah, Stefanie Kälin, Lucas F.R. Nascimento, Sarah Dietzen, Matthias Mann, Katharina Gerlach, Fabian Hosp, Ralf Palmisano, Stephen C. Woods, Verena B. Ott


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.

Publisher URL: http://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30493-X

DOI: 10.1016/j.cmet.2017.08.008

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