Your browser doesn't support javascript.
loading
Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction.
Schmidleithner, Lisa; Thabet, Yasser; Schönfeld, Eva; Köhne, 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; Schmidt, Susanne V; Nüssing, Simone; Sander, Jil; Ohkura, Naganari; Waha, Andreas; Sparwasser, Tim; Wunderlich, F Thomas; Förster, Irmgard; Ulas, Thomas; Weighardt, Heike; Sakaguchi, Shimon; Pfeifer, Alexander; Blüher, Matthias; Dannenberg, Andrew J; Ferreirós, Nerea; Muglia, Louis J; Wickenhauser, Claudia; Barry, Simon C; Schultze, Joachim L; Beyer, Marc.
Affiliation
  • Schmidleithner L; Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 27, 53127 Bonn, Germany; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Thabet Y; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Schönfeld E; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Köhne M; Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 27, 53127 Bonn, Germany; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Sommer D; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Abdullah Z; Institute of Experimental Immunology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
  • Sadlon T; Molecular Immunology, Robinson Research Institute, University of Adelaide, Norwich Centre, 55 King William St, North Adelaide, SA 5006, Australia.
  • Osei-Sarpong C; Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 27, 53127 Bonn, Germany; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Subbaramaiah K; Department of Medicine, Weill Cornell Medical College, 525 E. 68(th) Street, New York, NY 10065, USA.
  • Copperi F; Institute of Pharmacology and Toxicology, University of Bonn, 53127 Bonn, Germany.
  • Haendler K; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany; PRECISE, Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Ge
  • Varga T; Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 27, 53127 Bonn, Germany.
  • Schanz O; LIMES-Institute, Immunology & Environment, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Bourry S; Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 27, 53127 Bonn, Germany.
  • Bassler K; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Krebs W; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Peters AE; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany; Institute of Experimental Immunology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
  • Baumgart AK; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany; Institute of Experimental Immunology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
  • Schneeweiss M; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Klee K; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Schmidt SV; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Nüssing S; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Sander J; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Ohkura N; Laboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
  • Waha A; Department of Neuropathology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
  • Sparwasser T; Institute for Medical Microbiology and Hygiene (IMMH), Johannes Gutenberg-University Mainz, Obere Zahlbacherstr. 67, 55131 Mainz, Germany.
  • Wunderlich FT; Max Planck Institute for Metabolism Research, Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), Gleueler Str. 50, 50931 Cologne, Germany.
  • Förster I; LIMES-Institute, Immunology & Environment, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Ulas T; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Weighardt H; LIMES-Institute, Immunology & Environment, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany.
  • Sakaguchi S; Laboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
  • Pfeifer A; Institute of Pharmacology and Toxicology, University of Bonn, 53127 Bonn, Germany.
  • Blüher M; Department of Medicine, University of Leipzig, Liebigstraße 20, 04103 Leipzig, Germany.
  • Dannenberg AJ; Department of Medicine, Weill Cornell Medical College, 525 E. 68(th) Street, New York, NY 10065, USA.
  • Ferreirós N; Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
  • Muglia LJ; Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Wickenhauser C; Institute for Pathology, Martin-Luther University Halle - Wittenberg, Magdeburger Str. 14, 06112 Halle (Saale), Germany.
  • Barry SC; Molecular Immunology, Robinson Research Institute, University of Adelaide, Norwich Centre, 55 King William St, North Adelaide, SA 5006, Australia.
  • Schultze JL; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany; PRECISE, Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Ge
  • Beyer M; Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 27, 53127 Bonn, Germany; LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, Germany; PRECISE, Platform for Single Cell Ge
Immunity ; 50(5): 1232-1248.e14, 2019 05 21.
Article in En | MEDLINE | ID: mdl-31027998
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.
Subject(s)
Key words
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Database: MEDLINE Main subject: Dinoprostone / Hydroxyprostaglandin Dehydrogenases / T-Lymphocytes, Regulatory / Intra-Abdominal Fat Limits: Animals / Humans / Male Language: En Year: 2019 Type: Article
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Database: MEDLINE Main subject: Dinoprostone / Hydroxyprostaglandin Dehydrogenases / T-Lymphocytes, Regulatory / Intra-Abdominal Fat Limits: Animals / Humans / Male Language: En Year: 2019 Type: Article