Antigen- and Cytokine-Driven Accumulation of Regulatory T Cells in Visceral Adipose Tissue of Lean Mice

• Published in: Cell metabolism 2015-04, Vol.21 (4), p.543-557
• Main Authors: Kolodin, Dmitriy, van Panhuys, Nicolas, Li, Chaoran, Magnuson, Angela M., Cipolletta, Daniela, Miller, Christine M., Wagers, Amy, Germain, Ronald N., Benoist, Christophe, Mathis, Diane
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; CD4-Positive T-Lymphocytes - immunology; Cytokines - immunology; Immunohistochemistry; Interleukin-33 - immunology; Intra-Abdominal Fat - cytology; Intra-Abdominal Fat - immunology; Male; Mice; Models, Immunological; Obesity - drug therapy; Obesity - immunology; Thymocytes - immunology
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2015.03.005

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. [Display omitted] •VAT Tregs are generated in the thymus in the first weeks of life•VAT Tregs of lean mice show clonal micro-expansions and enhanced survival rates•Retention/accumulation depends on in situ recognition of an MHCII-restricted antigen(s)•The VAT Treg population of lean mice depends on and is potently expanded by IL-33 Kolodin et al. carefully characterize the origins of visceral adipose tissue regulatory T cells, which have beneficial metabolic effects in lean mice. They show that these cells are seeded from the thymus soon after birth and that their accumulation depends on local antigens and mediators, notably interleukin-33.