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Kälin, S. ; Becker, M. ; Ott, V. ; Serr, I. ; Hosp, F.* ; Mollah, M.M.H. ; Keipert, S. ; Lamp, D. ; Rohner-Jeanrenaud, F.* ; Flynn, V.K. ; Scherm, M.G. ; Nascimento, L.F.R. ; Gerlach, K.* ; Popp, V.* ; Dietzen, S.* ; Bopp, T.* ; Krishnamurthy, P.* ; Kaplan, M.H.* ; Serrano, M.* ; Woods, S.C.* ; Tripal, P.* ; Palmisano, R.* ; Jastroch, M. ; Blüher, M.* ; Wolfrum, C.* ; Weigmann, B.* ; Ziegler, A.-G. ; Mann, M.* ; Tschöp, M.H. ; Daniel, C.

A Stat6/Pten axis links regulatory T cells with adipose tissue function.

Cell Metab. 26, 475-492.e7 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Borcs6 ; C17orf59 ; Foxp3 ; Pten ; Stat6 ; T Cells ; Tregs ; Adipose Tissue Function ; Cold Exposure ; Metabolic Function ; Metabolism ; Regulatory T cells
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 26, Issue: 3, Pages: 475-492.e7 Article Number: , Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Type 1 Diabetes Immunology (TDI)
Institute of Diabetes Research Type 1 (IDF)