Schmidleithner, Lisa, Thabet, Yasser, Schoenfeld, Eva, Koehne, Maren, Sommer, Daniel, Abdullah, Zeinab, Sadlon, Timothy, Osei-Sarpong, Collins, Subbaramaiah, Kotha, Copperi, Francesca, Haendler, Kristian, Varga, Tamas, Schanz, Oliver, Bourry, Svenja, Bassler, Kevin, Krebs, Wolfgang, Peters, Annika E., Baumgart, Ann-Kathrin, Schneeweiss, Maria, Klee, Kathrin ORCID: 0000-0003-2408-1282, Schmidt, Susanne V., Nuessing, Simone, Sander, Jil, Ohkura, Naganari, Waha, Andreas, Sparwasser, Tim ORCID: 0000-0001-5645-902X, Wunderlich, F. Thomas, Foerster, Irmgard, Ulas, Thomas, Weighardt, Heike, Sakaguchi, Shimon, Pfeifer, Alexander, Blueher, Matthias, Dannenberg, Andrew J., Ferreiros, Nerea, Muglia, Louis J., Wickenhauser, Claudia, Barry, Simon C., Schultze, Joachim L. and Beyer, Marc ORCID: 0000-0001-9704-148X (2019). Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction. Immunity, 50 (5). S. 1232 - 1263. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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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-2 (PGE(2)) into the metabolite 15-keto PGE(2), was highly expressed in Treg cells, particularly those in visceral adipose tissue (VAT). Nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR gamma)-induced HPGD expression in VAT Treg cells, and consequential Treg-cell-mediated generation of 15-keto PG E2 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schmidleithner, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thabet, YasserUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoenfeld, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koehne, MarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sommer, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abdullah, ZeinabUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sadlon, TimothyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osei-Sarpong, CollinsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Subbaramaiah, KothaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Copperi, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haendler, KristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Varga, TamasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schanz, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bourry, SvenjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bassler, KevinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krebs, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, Annika E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumgart, Ann-KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneeweiss, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klee, KathrinUNSPECIFIEDorcid.org/0000-0003-2408-1282UNSPECIFIED
Schmidt, Susanne V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuessing, SimoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sander, JilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ohkura, NaganariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waha, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sparwasser, TimUNSPECIFIEDorcid.org/0000-0001-5645-902XUNSPECIFIED
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foerster, IrmgardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ulas, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weighardt, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sakaguchi, ShimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfeifer, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blueher, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dannenberg, Andrew J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferreiros, NereaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muglia, Louis J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wickenhauser, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barry, Simon C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schultze, Joachim L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beyer, MarcUNSPECIFIEDorcid.org/0000-0001-9704-148XUNSPECIFIED
URN: urn:nbn:de:hbz:38-148036
DOI: 10.1016/j.immuni.2019.03.014
Journal or Publication Title: Immunity
Volume: 50
Number: 5
Page Range: S. 1232 - 1263
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4180
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REGULATORY T-CELLS; 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE; PPAR-GAMMA; REG CELLS; EXPRESSION; INHIBITION; FAT; ACCUMULATION; METHYLATION; MECHANISMSMultiple languages
ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14803

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