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Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction.
- Source :
-
Immunity [Immunity] 2019 May 21; Vol. 50 (5), pp. 1232-1248.e14. Date of Electronic Publication: 2019 Apr 23. - Publication Year :
- 2019
-
Abstract
- Regulatory T cells (Treg cells) are important for preventing autoimmunity and maintaining tissue homeostasis, but whether Treg cells can adopt tissue- or immune-context-specific suppressive mechanisms is unclear. Here, we found that the enzyme hydroxyprostaglandin dehydrogenase (HPGD), which catabolizes prostaglandin E <subscript>2</subscript> (PGE <subscript>2</subscript> ) into the metabolite 15-keto PGE <subscript>2</subscript> , was highly expressed in Treg cells, particularly those in visceral adipose tissue (VAT). Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ)-induced HPGD expression in VAT Treg cells, and consequential Treg-cell-mediated generation of 15-keto PGE <subscript>2</subscript> suppressed conventional T cell activation and proliferation. Conditional deletion of Hpgd in mouse Treg cells resulted in the accumulation of functionally impaired Treg cells specifically in VAT, causing local inflammation and systemic insulin resistance. Consistent with this mechanism, humans with type 2 diabetes showed decreased HPGD expression in Treg cells. These data indicate that HPGD-mediated suppression is a tissue- and context-dependent suppressive mechanism used by Treg cells to maintain adipose tissue homeostasis.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- 3T3 Cells
Animals
Cell Line
Diabetes Mellitus, Type 2 metabolism
HEK293 Cells
Homeostasis immunology
Humans
Hydroxyprostaglandin Dehydrogenases genetics
Insulin Resistance genetics
Intra-Abdominal Fat cytology
Jurkat Cells
Lymphocyte Activation immunology
Male
Mice
Mice, Knockout
STAT5 Transcription Factor metabolism
Dinoprostone analogs & derivatives
Dinoprostone metabolism
Hydroxyprostaglandin Dehydrogenases metabolism
Intra-Abdominal Fat immunology
T-Lymphocytes, Regulatory enzymology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 50
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 31027998
- Full Text :
- https://doi.org/10.1016/j.immuni.2019.03.014