Interferon Response Factor 3 is essential for house dust mite-induced airway allergy
Marichal, Thomas ; ; Mesnil, Claire et al
in Journal of Allergy and Clinical Immunology (The) (2010), 126(4), 836-844
IRF3, mainly known as a central orchestrator of antiviral responses, is required for proallergic functions of dendritic cells in response to aeroallergens. Thus, this study demonstratively identifies a ... [more ▼]
IRF3, mainly known as a central orchestrator of antiviral responses, is required for proallergic functions of dendritic cells in response to aeroallergens. Thus, this study demonstratively identifies a new pathway potentially implicated in the etiology of airway allergy [less ▲]Detailed reference viewed: 103 (38 ULg)
Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response.
; ; et al
in European Journal of Immunology (2005), 35(5), 1491-1500
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 ... [more ▼]
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 [less ▲]Detailed reference viewed: 10 (2 ULg)
Prostaglandin D2 affects the maturation of human monocyte-derived dendritic cells: consequence on the polarization of naive Th cells.
; Bureau, Fabrice ; et al
in Journal of Immunology (2003), 170(10), 4943-52
Among the factors produced at inflammatory sites and those capable of modulating dendritic cell (DC) functions, PGD(2) may be important in the outcome of immune responses. The biological roles for PGD(2 ... [more ▼]
Among the factors produced at inflammatory sites and those capable of modulating dendritic cell (DC) functions, PGD(2) may be important in the outcome of immune responses. The biological roles for PGD(2) are in part effected through two plasma membrane G protein-coupled receptors: the D prostanoid (DP) receptor and the chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes (CRTH2). In this report, we studied the effects of PGD(2) and of its major physiological metabolite, 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), on the functions of human monocyte-derived DC. First, we show that PGD(2) exerts in vitro chemotactic effects on monocytes via CRTH2 activation while it inhibits the chemokine-driven migration of monocyte-derived DC through DP. We also report that PGD(2) and 15d-PGJ(2) alter the LPS- and allergen-induced DC maturation and enhance the CD80/CD86 ratio on mature DC in a DP- and CRTH2-independent manner. Moreover, PGD(2) and 15d-PGJ(2) strongly reduce the secretion of the Th1 promoting cytokine IL-12 and affect the synthesis of chemokines involved in Th1 cell chemotaxis, particularly CXCL10. Inhibition of cytokine/chemokine secretion implicates at least in part DP, but not CRTH2. The effects exerted by PGD(2) are associated with the phosphorylation of CREB, but do not parallel with the deactivation of the NF-kappa B and mitogen-activated protein kinase pathways. In contrast, 15d-PGJ(2) seems to target other cellular proteins. Finally, in a model of Th CD45RA(+) differentiation induced by allergen- and superantigen-pulsed DC, PGD(2) impacts on the orientation of the immune response by favoring a Th2 response [less ▲]Detailed reference viewed: 26 (4 ULg)
Prostaglandin D2 inhibits the production of interleukin-12 in murine dendritic cells through multiple signaling pathways.
; ; Bureau, Fabrice et al
in European Journal of Immunology (2003), 33(4), 889-898
Prostaglandin (PG) D(2), and its metabolites, are known to be important mediators during acute and chronic inflammation. However, their functions during the early phases of the immune response are poorly ... [more ▼]
Prostaglandin (PG) D(2), and its metabolites, are known to be important mediators during acute and chronic inflammation. However, their functions during the early phases of the immune response are poorly documented. In the present study, we show that PGD(2 )inhibits, in a dose-dependent manner, the CD40- and LPS-induced secretion of the Th1-driving factor IL-12 by murine splenic dendritic cells (DC), the most potent antigen-presenting cells. The inhibition of IL-12 production is mediated only in part by the cell surface G alpha s protein-coupled D prostanoid receptor (termed DP1) but not by the G alpha i protein-coupled DP receptor, DP2. We show that recruitment of DP1 in DC results in the activation of a cyclic AMP/protein kinase A pathway that is partially responsible for the inhibition of IL-12 production. We also suggest that the DP1-independent effects exerted by PGD(2) on IL-12 production may be due to the action of ist PGJ(2), but not PGF(2)alpha, metabolites. Electrophoretic mobility shift assays demonstrated that PGD(2) affects NF-kappa B activation through (the) DP1-independent pathway(s). Together these data suggest that PGD(2), by interacting with DP1 and by binding to other target cellular proteins, may regulate immune responses by affecting IL-12 production in DC [less ▲]Detailed reference viewed: 36 (1 ULg)