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


Journal

European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201

Informations de publication

Date de publication:
02 2019
Historique:
received: 25 02 2018
revised: 09 11 2018
accepted: 17 12 2018
pubmed: 20 12 2018
medline: 20 5 2020
entrez: 20 12 2018
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30566246
doi: 10.1002/eji.201847570
doi:

Substances chimiques

Antigens, Differentiation 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

336-347

Subventions

Organisme : Canadian Diabetes Association
ID : OG-3-14-4460-ML
Pays : International
Organisme : CIHR
Pays : Canada

Informations de copyright

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Auteurs

Dan Wu (D)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Jonathan M Han (JM)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Xin Yu (X)

Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.

Avery J Lam (AJ)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Romy E Hoeppli (RE)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Anne M Pesenacker (AM)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Qing Huang (Q)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Virginia Chen (V)

Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.

Cate Speake (C)

Diabetes Clinical Research Program, Benaroya Research Institute, Seattle, WA, USA.

Ekua Yorke (E)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
Richmond Metabolic and Bariatric Surgery Program, Richmond Hospital, Richmond, BC, Canada.

Nam Nguyen (N)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
Richmond Metabolic and Bariatric Surgery Program, Richmond Hospital, Richmond, BC, Canada.

Sharadh Sampath (S)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
Richmond Metabolic and Bariatric Surgery Program, Richmond Hospital, Richmond, BC, Canada.

David Harris (D)

Richmond Metabolic and Bariatric Surgery Program, Richmond Hospital, Richmond, BC, Canada.
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

Megan K Levings (MK)

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada.

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