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A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function.
Stefanie Kälin1, Maike Becker2, Verena B Ott3
1Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München and Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 85748 Munich, Germany; German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany.
Cell Metabolism
|September 7, 2017
Summary
Environmental factors like cold exposure and diet influence T-cells, promoting regulatory T-cell (Treg) induction. This study reveals a T-cell specific pathway linking these stimuli to Treg function and adipose tissue health.
Area of Science:
- Immunology
- Metabolic Health
- Adipose Tissue Biology
Background:
- Obesity and type 2 diabetes involve metabolic dysfunction and adipose tissue inflammation.
- Foxp3+ regulatory T cells (Tregs) are crucial for maintaining tissue homeostasis and suppressing inflammation.
- The role of T cells in mediating environmental influences on adipocyte function is not well understood.
Purpose of the Study:
- To investigate how environmental factors, such as sympathetic nervous system activation, influence T cell function and adipose tissue homeostasis.
- To elucidate the molecular mechanisms by which T cells link environmental cues to Treg induction and adipose tissue function.
Main Methods:
- In vitro and in vivo Treg induction assays.
- Analysis of CD4+ T cell proteomes following cold exposure or beta3-adrenergic receptor (ADRB3) stimulation.
- Loss- and gain-of-function studies, including Treg depletion and adoptive transfers.
- Investigation of the Stat6/Pten signaling axis in T cells.
Main Results:
- Cold exposure, ADRB3 stimulation, and high-calorie diets enhance Treg induction.
- CD4+ T cells show increased expression of Foxp3 regulatory networks upon cold or ADRB3 stimulation.
- C17orf59, a regulator of mTORC1 activity, is upregulated in CD4+ T cells, contributing to Treg induction.
- A T cell-specific Stat6/Pten axis mediates the link between environmental stimuli and Treg induction, impacting adipose tissue function.
Conclusions:
- Environmental stimuli that enhance sympathetic tone promote Treg induction through a T cell-specific Stat6/Pten pathway.
- Tissue-specific Tregs play a critical role in maintaining adipose tissue function.
- This study provides a novel mechanistic model for how environmental factors influence metabolic health via immune cell regulation.
Keywords:
Borcs6C17orf59Foxp3PTENSTAT6T cellsTregsadipose tissue functioncold exposuremetabolic functionmetabolismregulatory T cellsMore Related Videos
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