title: Prostaglandin E2 and T cells: friends or foes?
abstract: Our understanding of the key players involved in the differential regulation of T-cell responses during inflammation, infection and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. With respect to this, the inhibitory role of the lipid mediator prostaglandin E(2) (PGE(2)) in T-cell immunity has been documented since the 1970s. Studies that ensued investigating the underlying mechanisms substantiated the suppressive function of micromolar concentrations of PGE(2) in T-cell activation, proliferation, differentiation and migration. However, the past decade has seen a revolution in this perspective, since nanomolar concentrations of PGE(2) have been shown to potentiate Th1 and Th17 responses and aid in T-cell proliferation. The understanding of concentration-specific effects of PGE(2) in other cell types, the development of mice deficient in each subtype of the PGE(2) receptors (EP receptors) and the delineation of signalling pathways mediated by the EP receptors have enhanced our understanding of PGE(2) as an immune-stimulator. PGE(2) regulates a multitude of functions in T-cell activation and differentiation and these effects vary depending on the micro-environment of the cell, maturation and activation state of the cell, type of EP receptor involved, local concentration of PGE(2) and whether it is a homeostatic or inflammatory scenario. In this review, we compartmentalize the various aspects of this complex relationship of PGE(2) with T lymphocytes. Given the importance of this molecule in T-cell activation, we also address the possibility of using EP receptor antagonism as a potential therapeutic approach for some immune disorders.
authors.affiliation: Department of Molecular Biology, Centro de Biología Molecular Severo Ochoa, UAM-CSIC, Madrid, Spain. vinatha56@gmail.com
authors.forename: Vinatha
authors.initials: V
authors.lastname: Sreeramkumar
authors.forename: Manuel
authors.initials: M
authors.lastname: Fresno
authors.forename: Natalia
authors.initials: N
authors.lastname: Cuesta
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D015232:Dinoprostone / Q000276:immunology* / Q000378:metabolism*; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018078:Receptors, Prostaglandin E; D015232:Dinoprostone