1. A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function.
- Author
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Kälin S, Becker M, Ott VB, Serr I, Hosp F, Mollah MMH, Keipert S, Lamp D, Rohner-Jeanrenaud F, Flynn VK, Scherm MG, Nascimento LFR, Gerlach K, Popp V, Dietzen S, Bopp T, Krishnamurthy P, Kaplan MH, Serrano M, Woods SC, Tripal P, Palmisano R, Jastroch M, Blüher M, Wolfrum C, Weigmann B, Ziegler AG, Mann M, Tschöp MH, and Daniel C
- Subjects
- Animals, Cold Temperature, Female, Forkhead Transcription Factors metabolism, Mice, Inbred BALB C, Proteome metabolism, Receptors, Adrenergic, beta metabolism, Signal Transduction, T-Lymphocytes, Regulatory metabolism, Uncoupling Protein 1 metabolism, Adipose Tissue, Brown metabolism, Adipose Tissue, White metabolism, PTEN Phosphohydrolase metabolism, STAT6 Transcription Factor metabolism
- Abstract
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., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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