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@ARTICLE{Schmidleithner:140709,
author = {Schmidleithner, Lisa and Thabet, Yasser and Schönfeld, Eva
and Köhne, Maren and Sommer, Daniel and Abdullah, Zeinab
and Sadlon, Timothy and Osei-Sarpong, Collins and
Subbaramaiah, Kotha and Copperi, Francesca and Haendler,
Kristian and Varga, Tamas and Schanz, Oliver and Bourry,
Svenja and Bassler, Kevin and Krebs, Wolfgang and Peters,
Annika E and Baumgart, Ann-Kathrin and Schneeweiss, Maria
and Klee, Kathrin and Schmidt, Susanne V and Nüssing,
Simone and Sander, Jil and Ohkura, Naganari and Waha,
Andreas and Sparwasser, Tim and Wunderlich, F Thomas and
Förster, Irmgard and Ulas, Thomas and Weighardt, Heike and
Sakaguchi, Shimon and Pfeifer, Alexander and Blüher,
Matthias and Dannenberg, Andrew J and Ferreirós, Nerea and
Muglia, Louis J and Wickenhauser, Claudia and Barry, Simon C
and Schultze, Joachim L and Beyer, Marc},
title = {{E}nzymatic {A}ctivity of {HPGD} in {T}reg {C}ells
{S}uppresses {T}conv {C}ells to {M}aintain {A}dipose
{T}issue {H}omeostasis and {P}revent {M}etabolic
{D}ysfunction.},
journal = {Immunity},
volume = {50},
number = {5},
issn = {1074-7613},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2020-07031},
pages = {1232-1248.e14},
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 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.},
keywords = {3T3 Cells / Animals / Cell Line / Diabetes Mellitus, Type
2: metabolism / Dinoprostone: analogs $\&$ derivatives /
Dinoprostone: metabolism / HEK293 Cells / Homeostasis:
immunology / Humans / Hydroxyprostaglandin Dehydrogenases:
genetics / Hydroxyprostaglandin Dehydrogenases: metabolism /
Insulin Resistance: genetics / Intra-Abdominal Fat: cytology
/ Intra-Abdominal Fat: immunology / Jurkat Cells /
Lymphocyte Activation: immunology / Male / Mice / Mice,
Knockout / STAT5 Transcription Factor: metabolism /
T-Lymphocytes, Regulatory: enzymology / T-Lymphocytes,
Regulatory: immunology / STAT5 Transcription Factor (NLM
Chemicals) / 15-ketoprostaglandin E2 (NLM Chemicals) /
Hydroxyprostaglandin Dehydrogenases (NLM Chemicals) /
Dinoprostone (NLM Chemicals)},
cin = {AG Beyer / AG Alamoudi / Schultze - PRECISE},
ddc = {610},
cid = {I:(DE-2719)1013035 / I:(DE-2719)1013012 /
I:(DE-2719)1013031},
pnm = {341 - Molecular Signaling (POF3-341) / 342 - Disease
Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-341 / G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31027998},
doi = {10.1016/j.immuni.2019.03.014},
url = {https://pub.dzne.de/record/140709},
}