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

Kaelin 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, Blueher M, Wolfrum C, Weigmann B, Ziegler AG, Mann M, Tschoep MH, Daniel C (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 26

Pages Range: 475-492.e7

Journal Issue: 3

DOI: 10.1016/j.cmet.2017.08.008

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.

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Additional Organisation(s)

Involved external institutions

Johannes Gutenberg-Universität Mainz (JGU) Germany (DE) Indiana University – Purdue University Indianapolis United States (USA) (US) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) University of Cincinnati United States (USA) (US) Technische Universität München (TUM) Germany (DE) Universität Leipzig Germany (DE) École Polytechnique Fédérale de Lausanne (EPFL) Switzerland (CH) Deutsches Zentrum für Diabetesforschung e.V. (DZD) Germany (DE) Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry Germany (DE) University of Geneva / Université de Genève (UNIGE) Switzerland (CH)

How to cite

APA:

Kaelin, S., Becker, M., Ott, V.B., Serr, I., Hosp, F., Mollah, M.M.H.,... Daniel, C. (2017). A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function. Cell Metabolism, 26(3), 475-492.e7. https://dx.doi.org/10.1016/j.cmet.2017.08.008

MLA:

Kaelin, Stefanie, et al. "A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function." Cell Metabolism 26.3 (2017): 475-492.e7.

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