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

MPG-Autoren
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Hosp,  Fabian
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Zitation

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


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-002D-FFC1-4
Zusammenfassung
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.