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Eur J Immunol. 2018 Dec 19. doi: 10.1002/eji.201847570. [Epub ahead of print]

Characterization of regulatory T cells in obese omental adipose tissue in humans.

Author information

1
Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
2
BC Children's Hospital Research Institute, Vancouver, BC, Canada.
3
Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.
4
Diabetes Clinical Research Program, Benaroya Research Institute, Seattle, WA, USA.
5
Richmond Metabolic and Bariatric Surgery Program, Richmond Hospital, Richmond, BC, Canada.
6
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

Abstract

Obesity-associated visceral adipose tissue (AT) inflammation promotes insulin resistance and type 2 diabetes (T2D). In mice, lean visceral AT is populated with anti-inflammatory cells, notably regulatory T cells (Tregs) expressing the IL-33 receptor ST2. Conversely, obese AT contains fewer Tregs and more proinflammatory cells. In humans, however, there is limited evidence for a similar pattern of obesity-associated immunomodulation. We used flow cytometry and mRNA quantification to characterize human omental AT in 29 obese subjects, 18 of whom had T2D. Patients with T2D had increased proportions of inflammatory cells, including M1 macrophages, with positive correlations to body mass index. In contrast, Treg frequencies negatively correlated to body mass index but were comparable between T2D and non-T2D individuals. Compared to human thymic Tregs, omental AT Tregs expressed similar levels of FOXP3, CD25, IKZF2, and CTLA4, but higher levels of PPARG, CCR4, PRDM1, and CXCL2. ST2, however, was not detectable on omental AT Tregs from lean or obese subjects. This is the first comprehensive investigation into how omental AT immunity changes with obesity and T2D in humans, revealing important similarities and differences to paradigms in mice. These data increase our understanding of how pathways of immune regulation could be targeted to ameliorate AT inflammation in humans.

KEYWORDS:

Adipose tissue; IL-33; Immune regulation; Metabolism; Regulatory T cells (Tregs); Type 2 diabetes (T2D)

PMID:
30566246
DOI:
10.1002/eji.201847570

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