Objectif
Inflamatory bowel diseases (IBD) are systemic diseases characterized by intestinal inflamation and extra-intestinal manifestations. The compartimentalisation of inflammatory processes is driven by immunological mechanisms, in particular pertaining to homing and trafficking of immune cells. Intestinal Dendritic Cells (DC) are professional antigen presenting cells that recognize antigens and direct subsequent immune response. DC also dictate the type of T-cell immune response (e.g. pro-inflamatory or regulatory). In health, intestinal DC contribute to induction of immunological tolerance and control of immune activity in the gut. The Host Laboratory has provided evidence for the importance of immune compartmentalisation in IBD patients, since they have demonstrated an increased number of DC in inflamed mucosa of patients with IBD, increased activation of DC, and increased expression of both immune receptors and increased production of pathologically-related cytokines. Also, gut-homing DCs mark T-cells they stimulate with gut-homing markers. HYPOTHESIS In IBD, aberrant DC populations drive homing and functions of pathogenic T cells. AIMS 1. To examine changes in IBD (with and without extraintestinal manifestations) in the homing marker expression of DC 2. To identify the homing and functional properties of T-cells stimulated by subpopulations of DC in IBD. ANTICIPATED OUTCOMES In inflamed tissue, intestinal DC will have different homing markers and/or changed capacity to induce “gut homing” T cells. These changed profiles could be linked with different phenotypes of disease in patients with IBD. A greater understanding of this “post-code” system in DC and T-cells may lead to refinement of current therapies and development of more rational therapies for diseases at different anatomical sites and for different diseases, since it would be possible targeting the more easily accessible blood DC and T-cells destined to produce inflammation.
Champ scientifique
Thème(s)
Appel à propositions
FP7-PEOPLE-IEF-2008
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Régime de financement
MC-IEF - Intra-European Fellowships (IEF)Coordinateur
SW7 2AZ LONDON
Royaume-Uni