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

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Stefanie Kälin, Maike Becker, Verena B Ott, Isabelle Serr, Fabian Hosp, Mohammad M H Mollah, Susanne Keipert, Daniel Lamp, Francoise Rohner-Jeanrenaud, Victoria K Flynn, Martin G Scherm, Lucas F R Nascimento, Katharina Gerlach, Vanessa Popp, Sarah Dietzen, Tobias Bopp, Purna Krishnamurthy, Mark H Kaplan, Manuel Serrano, Stephen C Woods & 10 more Philipp Tripal, Ralf Palmisano, Martin Jastroch, Matthias Blüher, Christian Wolfrum, Benno Weigmann, Anette-Gabriele Ziegler, Matthias Mann, Matthias H Tschöp, Carolin Daniel

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.

Original languageEnglish
JournalCell Metabolism
Volume26
Issue number3
Pages (from-to)475-492.e7
ISSN1550-4131
DOIs
Publication statusPublished - 5 Sep 2017
Externally publishedYes

    Research areas

  • Journal Article

ID: 184323941