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Cell Metab. 2015 Apr 7;21(4):543-57. doi: 10.1016/j.cmet.2015.03.005.

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

Author information

1
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
2
Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
3
Joslin Diabetes Center, Boston, MA 02215, USA.
4
Joslin Diabetes Center, Boston, MA 02215, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
5
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston MA 02115, USA.
6
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston MA 02115, USA. Electronic address: cbdm@hms.harvard.edu.

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.

PMID:
25863247
PMCID:
PMC4747251
DOI:
10.1016/j.cmet.2015.03.005
[Indexed for MEDLINE]
Free PMC Article

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