TY  - JOUR
AU  - Schmidleithner, Lisa
AU  - Thabet, Yasser
AU  - Schönfeld, Eva
AU  - Köhne, Maren
AU  - Sommer, Daniel
AU  - Abdullah, Zeinab
AU  - Sadlon, Timothy
AU  - Osei-Sarpong, Collins
AU  - Subbaramaiah, Kotha
AU  - Copperi, Francesca
AU  - Haendler, Kristian
AU  - Varga, Tamas
AU  - Schanz, Oliver
AU  - Bourry, Svenja
AU  - Bassler, Kevin
AU  - Krebs, Wolfgang
AU  - Peters, Annika E
AU  - Baumgart, Ann-Kathrin
AU  - Schneeweiss, Maria
AU  - Klee, Kathrin
AU  - Schmidt, Susanne V
AU  - Nüssing, Simone
AU  - Sander, Jil
AU  - Ohkura, Naganari
AU  - Waha, Andreas
AU  - Sparwasser, Tim
AU  - Wunderlich, F Thomas
AU  - Förster, Irmgard
AU  - Ulas, Thomas
AU  - Weighardt, Heike
AU  - Sakaguchi, Shimon
AU  - Pfeifer, Alexander
AU  - Blüher, Matthias
AU  - Dannenberg, Andrew J
AU  - Ferreirós, Nerea
AU  - Muglia, Louis J
AU  - Wickenhauser, Claudia
AU  - Barry, Simon C
AU  - Schultze, Joachim L
AU  - Beyer, Marc
TI  - Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction.
JO  - Immunity
VL  - 50
IS  - 5
SN  - 1074-7613
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2020-07031
SP  - 1232-1248.e14
PY  - 2019
AB  - 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 E2 (PGE2) into the metabolite 15-keto PGE2, 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 PGE2 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.
KW  - 3T3 Cells
KW  - Animals
KW  - Cell Line
KW  - Diabetes Mellitus, Type 2: metabolism
KW  - Dinoprostone: analogs & derivatives
KW  - Dinoprostone: metabolism
KW  - HEK293 Cells
KW  - Homeostasis: immunology
KW  - Humans
KW  - Hydroxyprostaglandin Dehydrogenases: genetics
KW  - Hydroxyprostaglandin Dehydrogenases: metabolism
KW  - Insulin Resistance: genetics
KW  - Intra-Abdominal Fat: cytology
KW  - Intra-Abdominal Fat: immunology
KW  - Jurkat Cells
KW  - Lymphocyte Activation: immunology
KW  - Male
KW  - Mice
KW  - Mice, Knockout
KW  - STAT5 Transcription Factor: metabolism
KW  - T-Lymphocytes, Regulatory: enzymology
KW  - T-Lymphocytes, Regulatory: immunology
KW  - STAT5 Transcription Factor (NLM Chemicals)
KW  - 15-ketoprostaglandin E2 (NLM Chemicals)
KW  - Hydroxyprostaglandin Dehydrogenases (NLM Chemicals)
KW  - Dinoprostone (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:31027998
DO  - DOI:10.1016/j.immuni.2019.03.014
UR  - https://pub.dzne.de/record/140709
ER  -