期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 2, 页码 482-487出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1423486112
关键词
obesity; inflammation; type 2 diabetes; regulatory T cell; Foxp3
资金
- NIH [R01 DK092541]
- Ellison Foundation (Boston)
- JPB Foundation
- Joslin Diabetes Center [P30DK36836]
A unique population of Foxp3(+)CD4(+) regulatory T (T-reg) cells resides in visceral adipose tissue (VAT) of lean mice, especially in the epididymal fat depot. VAT T-regs are unusual in their very high representation within the CD4(+) T-cell compartment, their transcriptome, and their repertoire of antigen-specific T-cell receptors. They are important regulators of local and systemic inflammation and metabolism. The overall goal of this study was to learn how the VAT T-reg transcriptome adapts to different stimuli; in particular, its response to aging in lean mice, to metabolic perturbations associated with obesity, and to certain signaling events routed through PPAR gamma, the master-regulator of adipocyte differentiation. We show that the VAT T-reg signature is imposed early in life, well before age-dependent expansion of the adipose-tissue Treg population. VAT T-regs in obese mice lose the signature typical of lean individuals but gain an additional set of over-and underrepresented transcripts. This obese mouse VAT T-reg signature depends on phosphorylation of the serine residue at position 273 of PPAR gamma, in striking parallel to a pathway recently elucidated in adipocytes. These findings are important to consider in designing drugs to target type 2 diabetes and other features of the metabolic syndrome.
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