Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/120642
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Type: Journal article
Title: Enzymatic activity of HPGD in Treg cells Suppresses Tconv cells to maintain adipose tissue homeostasis and prevent metabolic dysfunction
Author: Schmidleithner, L.
Thabet, Y.
Schönfeld, E.
Köhne, M.
Sommer, D.
Abdullah, Z.
Sadlon, T.
Osei-Sarpong, C.
Subbaramaiah, K.
Copperi, F.
Haendler, K.
Varga, T.
Schanz, O.
Bourry, S.
Bassler, K.
Krebs, W.
Peters, A.
Baumgart, A.
Schneeweiss, M.
Klee, K.
et al.
Citation: Immunity, 2019; 50(5):1232-1248.e14
Publisher: Cell Press
Issue Date: 2019
ISSN: 1074-7613
1097-4180
Statement of
Responsibility: 
Lisa Schmidleithner, Yasser Thabet, Eva Schonfeld, Maren Kohne, Daniel Sommer ... Simon C. Barry ... et al.
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: Foxp3; HPGD; PGE(2); adipose tissue; regulatory T cells; suppressive function; type 2 diabetes
Rights: © 2019 Elsevier Inc.
RMID: 0030117418
DOI: 10.1016/j.immuni.2019.03.014
Grant ID: http://purl.org/au-research/grants/nhmrc/339123
http://purl.org/au-research/grants/nhmrc/565314
Appears in Collections:Medicine publications

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