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

Cell Metab. 2017 Sep 5;26(3):475-492.e7. doi: 10.1016/j.cmet.2017.08.008.


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.

Keywords: Borcs6; C17orf59; Foxp3; PTEN; STAT6; T cells; Tregs; adipose tissue function; cold exposure; metabolic function; metabolism; regulatory T cells.

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / metabolism*
  • Animals
  • Cold Temperature
  • Female
  • Forkhead Transcription Factors / metabolism
  • Mice, Inbred BALB C
  • PTEN Phosphohydrolase / metabolism*
  • Proteome / metabolism
  • Receptors, Adrenergic, beta / metabolism
  • STAT6 Transcription Factor / metabolism*
  • Signal Transduction
  • T-Lymphocytes, Regulatory / metabolism
  • Uncoupling Protein 1 / metabolism


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Proteome
  • Receptors, Adrenergic, beta
  • STAT6 Transcription Factor
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • PTEN Phosphohydrolase