title: Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response.
abstract: The local environment in which dendritic cells (DC) differentiate is important for the acquisition of their immunostimulatory properties. Since prostaglandin D(2) (PGD(2)), a major prostanoid produced during inflammatory reactions, is involved in the control of immune responses, its effect on the differentiation and functions of human monocyte-derived dendritic cells (MDDC) was studied. We show that DC differentiated in the presence of PGD(2) (PG/DC) have an unusual phenotype, with modifications in the expression of molecules involved in antigen (Ag) capture and presentation, leading to higher endocytic and Ag-processing activities. However, under conditions that necessitated Ag processing and presentation, PG/DC have an impaired ability to stimulate naive T cells, whereas superAg-pulsed DC efficiently promote their proliferation. Upon lipopolysaccharide or TNF-alpha/IL-1beta stimulation, PG/DC phenotypically mature but produce abnormal amounts of immunoregulatory cytokines (decreased IL-12p70/IL-10 ratio). Moreover, mature PG/DC fail to up-regulate the chemokine receptor CCR7 and show an impaired migration towards its ligand CCL19. Finally, PG/DC favor the differentiation of naive T cells toward Th2 cells, an effect dependent on IL-10 and inducible costimulator ligand expression by DC. Most of the herein described effects of PGD(2) on MDDC can be reproduced, usually with a higher efficacy, with a selective D prostanoid receptor (DP)1, but not DP2, agonist. Taken as a whole, these results demonstrate that PGD(2) impacts DC differentiation and functions, and extend the concept that it exerts important roles in immunity.
authors.affiliation: Inserm U416, Institut Fédératif de Recherche 17, Institut Pasteur de Lille, Lille, France. philippe.gosset@pasteur-lille.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
authors.forename: Muriel
authors.initials: M
authors.lastname: Pichavant
authors.forename: Christelle
authors.initials: C
authors.lastname: Faveeuw
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
authors.forename: André-Bernard
authors.initials: AB
authors.lastname: Tonnel
authors.forename: François
authors.initials: F
authors.lastname: Trottein
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D010641:Phenotype; D011457:Prostaglandins D / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C515370:CCR7 protein, human; D016207:Cytokines; D011457:Prostaglandins D; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine