6533b870fe1ef96bd12cfd31
RESEARCH PRODUCT
Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction.
Tim SparwasserKristian HaendlerKristian HaendlerKathrin KleeLouis J. MugliaAnnika E. PetersAnnika E. PetersThomas UlasTamas VargaSimone NüssingMarc BeyerMarc BeyerZeinab AbdullahF. Thomas WunderlichMatthias BlüherOliver SchanzJil SanderCollins Osei-sarpongCollins Osei-sarpongKevin BasslerSimon C. BarryShimon SakaguchiNerea FerreirósNaganari OhkuraAlexander PfeiferAndreas WahaMaren KöhneMaren KöhneSvenja BourryIrmgard FörsterKotha SubbaramaiahYasser ThabetFrancesca CopperiClaudia WickenhauserSusanne SchmidtMaria SchneeweissLisa SchmidleithnerLisa SchmidleithnerDaniel SommerWolfgang KrebsHeike WeighardtAndrew J. DannenbergEva A. SchönfeldTimothy SadlonAnn Kathrin BaumgartAnn Kathrin BaumgartJoachim L. SchultzeJoachim L. Schultzesubject
0301 basic medicineanalogs & derivatives [Dinoprostone]Malemetabolism [Diabetes Mellitus Type 2]Adipose tissueLymphocyte Activation15-ketoprostaglandin E2T-Lymphocytes RegulatoryJurkat cellsJurkat CellsMice0302 clinical medicineimmunology [Lymphocyte Activation]genetics [Insulin Resistance]STAT5 Transcription FactorHomeostasisImmunology and AllergyTissue homeostasisgenetics [Hydroxyprostaglandin Dehydrogenases]Mice Knockoutcytology [Intra-Abdominal Fat]enzymology [T-Lymphocytes Regulatory]FOXP3hemic and immune systems3T3 CellsCell biologyInfectious Diseases030220 oncology & carcinogenesisHydroxyprostaglandin Dehydrogenasesmedicine.symptomimmunology [T-Lymphocytes Regulatory]metabolism [STAT5 Transcription Factor]Immunologymetabolism [Dinoprostone]chemical and pharmacologic phenomenaInflammationIntra-Abdominal FatBiologyDinoprostoneCell Line03 medical and health sciencesmetabolism [Hydroxyprostaglandin Dehydrogenases]immunology [Homeostasis]medicineAnimalsHumansddc:610immunology [Intra-Abdominal Fat]HEK 293 cells030104 developmental biologyHEK293 CellsDiabetes Mellitus Type 2Cell cultureInsulin ResistanceHomeostasisdescription
Summary 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-05-01 |