Objective Dendritic cells (DCs) are essential for the instruction of adaptive immunity and for the pathogenesis of many inflammatory lung diseases. These cells sense the presence of exogenous and endogenous signals and initiate an immune response that is matched to the nature of the offending insult. Many environmental triggers of inflammatory lung diseases including allergens, cigarette smoke, fine dust particles or microbes induce signs of endoplasmic reticulum (ER) stress in lung cells. ER stress is characterized by an accumulation of unfolded proteins in the ER, which leads to an intracellular signalling cascade named unfolded protein response (UPR). Although it has been recently shown that the UPR is a constitutively active signalling pathway in DCs, it is unknown whether activation of the ER stress pathways in DCs contributes to the regulation of immune responses at mucosal sites.The foundations of this project lie in three crucial aspects of DCs: 1) DCs are important sensors of exogenous and endogenous danger signals in the lung, 2) DCs are active targets of the ER stress response, and 3) DCs are central coordinators of the immune response that leads to asthma. Based on these three aspects, we hypothesize that the presence of unfolded proteins in the ER acts as an endogenous danger signal that plays a fundamental role in the function of lung DCs and their involvement in inflammatory lung diseases.With this project, we will gain firm knowledge about the cellular events that coordinate the ER stress response to environmental triggers in DCs. By using innovative approaches, we will analyze the relevance of the UPR signalling in lung DC subsets in vivo. In addition, in light of previous findings reporting the genetic association between polymorphisms in the ER stress regulator ORMDL3 and asthma, we will formally evaluate the role of ORMDL3 in the development of lung inflammation. Fields of science medical and health sciencesclinical medicinepneumologyasthmanatural sciencesbiological sciencescell biologycell signalingnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologyengineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensors 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) FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2010-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator UNIVERSITEIT GENT EU contribution € 163 300,00 Address SINT PIETERSNIEUWSTRAAT 25 9000 Gent Belgium See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Activity type Higher or Secondary Education Establishments Administrative Contact Saskia Vanden Broeck (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
