title: Prostaglandin E2 signaling through E prostanoid receptor 2 impairs proliferative response of double negative regulatory T cells.
abstract: Limited data are available on the mechanisms that constrain the function of regulatory populations of T cells. Prostaglandin E2 (PGE2) is an endogenous membrane phospholipid metabolite that has important immunomodulatory effects on T cell function. Our previous microarray data indicated that E prostanoid receptor 2 (EP2), a receptor for PGE2, is expressed by regulatory alphabetaTCR(+) CD4(-) CD8(-) NK1.1(-) double negative T (DN Treg) cell clones but not by their non-regulatory natural mutants. Hence, the hypothesis that PGE2 may influence DN Treg cell proliferation and/or regulatory function was tested in this study. Our data indicate that PGE2 acts via the EP2 receptor on DN Treg cells to inhibit their proliferation, an effect reproduced by the EP2-specific agonist butaprost and abrogated by the EP2 antagonist AH6809. In contrast, PGE2 did not affect the ability of DN Treg cells to kill syngeneic CD8(+) T cells activated by allogeneic stimulation. Together, these findings suggest a role for PGE2 in limiting the expansion of DN Treg cells.
authors.affiliation: Multi-Organ Transplantation Program, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Boris P L
authors.initials: BP
authors.lastname: Lee
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Juvet
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015704:CD4 Antigens; D016827:CD8 Antigens; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism*; D018189:Immunomagnetic Separation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D044004:Xanthones / Q000494:pharmacology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D011448:Prostaglandin Antagonists; C545645:Ptger2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone