title: Additive effects of rapamycin and aspirin on dendritic cell allostimulatory capacity.
abstract: Acting as antigen presenting cells, mature dendritic cells (DCs) initiate both innate and adaptive alloimmune responses. However, immature DCs are weak immunostimulators and mediate tolerogenic effects under certain conditions. Tolerogenic activities of immature DCs can be enhanced by pharmacological agents. Here, we compared pharmacological DC preconditioning with rapamycin and aspirin, applied alone or in combination, on LPS-induced DC maturation and T-cell allostimulatory capacity. Preconditioning with aspirin but not rapamycin tended to reduce the number of mouse bone marrow-derived immature DCs expressing CD40 and major histocompatibility complex class II molecules upon LPS stimulation. Conversely, DC preconditioning with rapamycin, but not aspirin, reduced T-cell alloproliferative responses. A combination of rapamycin and aspirin was more effective than either drug applied alone with respect to inhibition of T-cell alloproliferation. The two agents in combination reduced numbers of CD4(+)IFN-γ(+) Th1 and CD4(+)IL-17(+) Th17 effector cells while maintaining Foxp3(+) regulatory T cells. These results suggest aspirin may moderately enhance rapamycin-mediated inhibition of DC allostimulatory capacity.
authors.affiliation: a Molecular Cardiology Laboratory, Department of Cardiology, Centre Hospitalier Universitaire Vaudois (CHUV) , Lausanne , Switzerland .
authors.forename: Marc-Estienne
authors.initials: ME
authors.lastname: Roehrich
authors.affiliation: b Transplantation Immunopathology Laboratory, Transplantation Centre, Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) , Lausanne , Switzerland , and.
authors.forename: Jean-Cristophe
authors.initials: JC
authors.lastname: Wyss
authors.affiliation: b Transplantation Immunopathology Laboratory, Transplantation Centre, Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) , Lausanne , Switzerland , and.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: b Transplantation Immunopathology Laboratory, Transplantation Centre, Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) , Lausanne , Switzerland , and.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
authors.affiliation: b Transplantation Immunopathology Laboratory, Transplantation Centre, Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) , Lausanne , Switzerland , and.
authors.forename: Dela
authors.initials: D
authors.lastname: Golshayan
authors.affiliation: a Molecular Cardiology Laboratory, Department of Cardiology, Centre Hospitalier Universitaire Vaudois (CHUV) , Lausanne , Switzerland .|c Molecular Cardiology Laboratory, Fondazione Cardiocentro Ticino , Lugano , Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vassalli
mesh_terms: D000818:Animals; D001241:Aspirin / Q000819:agonists / Q000494:pharmacology*; D019013:CD40 Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020123:Sirolimus / Q000819:agonists / Q000494:pharmacology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D001241:Aspirin; D020123:Sirolimus
keywords: Aspirin; IL-10; dendritic cell; rapamycin; regulatory T cell; tolerance