1. A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function
- Author
-
Françoise Rohner-Jeanrenaud, Ralf Palmisano, Martin Jastroch, Carolin Daniel, Anette-Gabriele Ziegler, Maike Becker, Martin G. Scherm, Mohammad M.H. Mollah, Benno Weigmann, Isabelle Serr, Victoria K. Flynn, Philipp Tripal, Tobias Bopp, Manuel Serrano, Stephen C. Woods, Lucas F. Nascimento, Daniel Lamp, Fabian Hosp, Matthias H. Tschöp, Sarah Dietzen, Katharina Gerlach, Matthias Blüher, Christian Wolfrum, Mark H. Kaplan, Matthias Mann, Vanessa Popp, Verena B. Ott, Purna Krishnamurthy, Stefanie Kälin, Susanne Keipert, and Rohner-Jeanrenaud, Françoise
- Subjects
0301 basic medicine ,PTEN ,Proteome ,Physiology ,Adipose tissue ,Stimulation ,mTORC1 ,Diet induced thermogenesis ,Borcs6 ,C17orf59 ,Foxp3 ,Pten ,Stat6 ,T Cells ,Tregs ,Adipose Tissue Function ,Cold Exposure ,Metabolic Function ,Metabolism ,Regulatory T cells ,T-Lymphocytes, Regulatory ,chemistry.chemical_compound ,0302 clinical medicine ,Adipose Tissue, Brown ,Adipocyte ,Uncoupling Protein 1 ,Tissue homeostasis ,STAT6 ,ddc:616 ,Mice, Inbred BALB C ,FOXP3 ,Forkhead Transcription Factors ,hemic and immune systems ,Cell biology ,Cold Temperature ,Female ,Metabolic function ,medicine.symptom ,Signal Transduction ,Adipose Tissue, White ,Cold exposure ,T cells ,chemical and pharmacologic phenomena ,Inflammation ,Biology ,Article ,03 medical and health sciences ,Receptors, Adrenergic, beta ,Adipose tissue function ,medicine ,Animals ,Molecular Biology ,PTEN Phosphohydrolase ,Cell Biology ,030104 developmental biology ,chemistry ,Immunology ,STAT6 Transcription Factor ,030217 neurology & neurosurgery - Abstract
Obesity and type 2 diabetes are associated with metabolic defects and adipose tissue inflammation. Foxp3(+) regulatory Tcells (Tregs) control tissue homeostasis by counteracting local inflammation. However, if and how Tcells 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 invitro and invivo. CD4(+) Tcell proteomes revealed higher expression of Foxp3 regulatory networks in response to cold or ADRB3 stimulation invivo reflecting Treg induction. Specifically, Ragulator-interacting protein C17orf59, which limits mTORC1 activity, was upregulated in CD4(+) Tcells by either ADRB3 stimulation or cold exposure, suggesting contribution to Treg induction. By loss- and gain-of-function studies, including Treg depletion and transfers invivo, we demonstrated that a Tcell-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.
- Published
- 2017
- Full Text
- View/download PDF