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

Stefanie Kälin; Maike Becker; Verena B Ott; Isabelle Serr; Fabian Hosp; Mohammad M H Mollah; Susanne Keipert; Daniel Lamp; Francoise Rohner-Jeanrenaud; Victoria K Flynn; Martin G Scherm; Lucas F R Nascimento; Katharina Gerlach; Vanessa Popp; Sarah Dietzen; Tobias Bopp; Purna Krishnamurthy; Mark H Kaplan; Manuel Serrano; Stephen C Woods; Philipp Tripal; Ralf Palmisano; Martin Jastroch; Matthias Blüher; Christian Wolfrum; Benno Weigmann; Anette-Gabriele Ziegler; Matthias Mann; Matthias H Tschöp; Carolin Daniel

doi:10.1016/j.cmet.2017.08.008

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

Stefanie Kälin, Maike Becker, Verena B Ott, Isabelle Serr, Fabian Hosp, Mohammad M H Mollah, Susanne Keipert, Daniel Lamp, Francoise Rohner-Jeanrenaud, Victoria K Flynn, Martin G Scherm, Lucas F R Nascimento, Katharina Gerlach, Vanessa Popp, Sarah Dietzen, Tobias Bopp, Purna Krishnamurthy, Mark H Kaplan, Manuel Serrano, Stephen C WoodsPhilipp Tripal, Ralf Palmisano, Martin Jastroch, Matthias Blüher, Christian Wolfrum, Benno Weigmann, Anette-Gabriele Ziegler, Matthias Mann, Matthias H Tschöp, Carolin Daniel

33 Citations (Scopus)

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.

Original language	English
Journal	Cell Metabolism
Volume	26
Issue number	3
Pages (from-to)	475-492.e7
ISSN	1550-4131
DOIs	https://doi.org/10.1016/j.cmet.2017.08.008
Publication status	Published - 5 Sept 2017
Externally published	Yes

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmet.2017.08.008

http://www.cell.com/article/S155041311730493X/pdf

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

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, A-G, Mann, M, Tschöp, MH & Daniel, C 2017, 'A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function', Cell Metabolism, vol. 26, no. 3, pp. 475-492.e7. https://doi.org/10.1016/j.cmet.2017.08.008

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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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AU - Kälin, Stefanie

AU - Becker, Maike

AU - Ott, Verena B

AU - Serr, Isabelle

AU - Hosp, Fabian

AU - Mollah, Mohammad M H

AU - Keipert, Susanne

AU - Lamp, Daniel

AU - Rohner-Jeanrenaud, Francoise

AU - Flynn, Victoria K

AU - Scherm, Martin G

AU - Nascimento, Lucas F R

AU - Gerlach, Katharina

AU - Popp, Vanessa

AU - Dietzen, Sarah

AU - Bopp, Tobias

AU - Krishnamurthy, Purna

AU - Kaplan, Mark H

AU - Serrano, Manuel

AU - Woods, Stephen C

AU - Tripal, Philipp

AU - Palmisano, Ralf

AU - Jastroch, Martin

AU - Blüher, Matthias

AU - Wolfrum, Christian

AU - Weigmann, Benno

AU - Ziegler, Anette-Gabriele

AU - Mann, Matthias

AU - Tschöp, Matthias H

AU - Daniel, Carolin

PY - 2017/9/5

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N2 - 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.

AB - 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.

KW - Journal Article

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DO - 10.1016/j.cmet.2017.08.008

M3 - Journal article

C2 - 28877454

SN - 1550-4131

VL - 26

SP - 475-492.e7

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -

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

Abstract

Keywords

UN SDGs

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