Adipose tissue macrophages induce PPARγ-high FOXP3(+) regulatory T cells

Sci Rep. 2015 Nov 19:5:16801. doi: 10.1038/srep16801.

Abstract

Numerous regulatory T cells (Tregs) are present in adipose tissues compared with other lymphoid or non-lymphoid tissues. Adipose Tregs regulate inflammatory state and insulin sensitivity. However, the mechanism that maintains Tregs in adipose tissue remains unclear. Here, we revealed the contribution of adipose tissue macrophages (ATMs) to the induction and proliferation of adipose Tregs. ATMs isolated from mice under steady state conditions induced Tregs with high expression of PPARγ compared with splenic dendritic cells in vitro. Furthermore, ATMs from obese mice prompted the differentiation of PPARγ low Tregs. Adoptive transfer of ATMs induced differentiation and proliferation of Tregs, whereas depletion of ATMs by clodronate-liposome resulted in reduction of adipose Tregs, in vivo. Deficiency of anti-inflammatory adipocytokine, Adipoq, resulted in small proportions of ATMs and adipose Tregs without alteration of other immune cells in vivo. Therefore, these data suggest that the abundance of Tregs in adipose tissue could be partly attributed to the ability of ATMs to induce PPARγ-expressing Tregs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / deficiency
  • Adiponectin / metabolism
  • Adipose Tissue / cytology*
  • Animals
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Clodronic Acid / pharmacology
  • Diet, High-Fat
  • Forkhead Transcription Factors / metabolism*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Male
  • Mice, Inbred C57BL
  • PPAR gamma / metabolism*
  • Phenotype
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Adiponectin
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • PPAR gamma
  • Clodronic Acid