Objective Allogeneic haematopoietic stem cell transplantation (HSCT) is an important curative therapy for a large number of hematological diseases. Graft versus host disease (GVHD) remains the major complication of allogeneic HSCT, which occurs in 40-60% of transplant recipients and could be directly responsible for 25% of transplant related mortality and a significant proportion of transplant related morbidity. Established immunosuppressive treatments are of limited efficacy and have significant side effects. Extracorporeal Phototherapy (ECP) is an effective treatment for GvHD. Importantly, infection and relapse rates are not increased in the course of ECP treatment. Hence, ECP is an exciting model to study tolerance mechanisms. ECP actions include apoptosis, cytokine modulation and the induction of regulatory T cells but the underlying mechanisms have not been revealed yet. Antigen presenting cells like dendritic cells (DCs) are thought to be important in mediating ECP effects. The project aims at comprehensively analysing ECP effects with special focus on the modulation of dendritic cells by ECP induced apoptotic cells. A unique modified skin explant model simulating ECP treatment for GvHD will be used to analyse immunoregulatory characteristics of DCs and T cells modified by apoptotic cells. Proteins known to carry regulatory potential will be assessed and mRNA expression arrays will be used to identify novel molecules involved in tolerance. The project will furthermore explore if ECP induced apoptotic cells have unique properties by comparing different methods of apoptosis induction. The skin explant model will be used in an antigen-specific context to clarify whether ECP actions are T cell clone specific. The last part of the project will analyse DNA polymorphisms of molecules identified during the course of the project to predict reponses to ECP in patients. In summary, ECP will be used as a model to study tolerance and derive novel tolerogenic strategies. Fields of science social sciencessociologydemographymortalitynatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineemergency medicinegraft versus host diseasemedical and health sciencesclinical medicinetransplantation Keywords Immunology Medical sciences graft-versus host photopheresis tolerance transplantation Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) PEOPLE-2007-2-2.ERG - Marie Curie Action: "European Reintegration Grants" Call for proposal FP7-PEOPLE-2007-2-2-ERG See other projects for this call Funding Scheme MC-ERG - European Re-integration Grants (ERG) Coordinator KLINIKUM DER UNIVERSITAET ZU KOELN EU contribution € 45 000,00 Address Kerpener Strasse 62 50937 Koeln Germany See on map Region Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Jutta Landvogt (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
