Antigen- and cytokine-driven accumulation of regulatory t cells in visceral adipose tissue of lean mice

Dmitriy Kolodin, Nicholas J. Van Panhuys, Chaoran Li, Angela M. Magnuson, Daniela Cipolletta, Christine M. Miller, Amy Wagers, Ronald N. Germain, Christophe Benoist, Diane Mathis

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Abstract

A unique population of Foxp3+CD4+ regulatory T (Treg) cells, with a distinct transcriptome and antigen-receptor repertoire, resides in visceral adipose tissue (VAT) of lean individuals. These cells regulate local inflammation and both local and systemic metabolic indices. Here we focus on expansion of the VAT Treg compartment in aging lean mice - assessing these cells' phenotypic conversion from conventional CD4+ T cells, influx from lymphoid organs, and local population dynamics. Our findings establish that the VAT Treg compartment is seeded from thymocytes generated during the first weeks of life and expands beyond 10 weeks of age due to indolent proliferation, of certain clones in particular, coupled with enhanced survival. Accumulation of VAT Tregs depends on the antigen(s) presented by MHC class-II molecules and soluble mediators, notably interleukin(IL)-33. Addressing such factors therapeutically promises novel approaches for harnessing Tregs to stem the growing epidemic of obesity and consequent metabolic abnormalities.

Original languageEnglish
Pages (from-to)543-557
Number of pages15
JournalCell Metabolism
Volume21
Issue number4
DOIs
Publication statusPublished - 7 Apr 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Kolodin, D., Van Panhuys, N. J., Li, C., Magnuson, A. M., Cipolletta, D., Miller, C. M., Wagers, A., Germain, R. N., Benoist, C., & Mathis, D. (2015). Antigen- and cytokine-driven accumulation of regulatory t cells in visceral adipose tissue of lean mice. Cell Metabolism, 21(4), 543-557. https://doi.org/10.1016/j.cmet.2015.03.005