Description du projet
Nouvelle perspective sur la pathogenèse de l’inflammation intestinale chronique
La transition épithélio-mésenchymateuse (TEM) est un processus par lequel les cellules épithéliales immobiles se convertissent en cellules mésenchymateuses migrantes, et joue un rôle central au cours du développement. Cependant, la TEM se réactive dans certaines affections, notamment le cancer, ce qui contribue à la transformation en tumeurs malignes, à la progression tumorale et à la résistance aux traitements. Le projet INFLEMT, financé par l’UE, s’intéresse au rôle de la TEM dans la maladie inflammatoire de l’intestin (MII), un trouble chronique du tube digestif. Les chercheurs étudieront la TEM dans le cadre de la MII et mettront en lumière son influence sur les cellules épithéliales intestinales et le développement de la fibrose. Étant donné la forte prévalence de la MII, les résultats génèreront de précieuses informations sur la pathogenèse de la maladie et pourraient aboutir à de nouvelles stratégies thérapeutiques.
Objectif
Inflammatory bowel disease (IBD) defines a group of chronic inflammatory disorders of the digestive tract, with ulcerative colitis and Crohn’s disease being its two major clinical manifestations, affecting 2.5 million people in Europe. The high prevalence of IBD in Europe and the multiple clinical challenges associated with a significant degree of unresponsiveness to anti-inflammatory therapies and development of complications requiring surgical intervention demand a deeper understanding of the cellular and molecular mechanisms underpinning IBD.
This project aims to understand the role of the process termed Epithelial–to–Mesenchymal Transition (EMT), an embryonic cellular trans-differentiation program re-launched in many pathological conditions, in the pathogenesis of IBD. EMT has in fact been detected in the inflamed intestinal mucosa and surrounding fibrotic areas of IBD patients and experimental models of colitis, however whether EMT functionally contributes to the pathogenesis of IBD is poorly understood.
The INFLEMT project aims to: 1) profile EMT in human IBD to identify its cellular features and correlation with the disease stage; 2) elucidate the impact of EMT on the integrity, functionality and regenerative capacity of the intestinal epithelial barrier; 3) explore the effects of EMT on fibrosis development and modulation of the immune response to assess its role in sustaining the chronic intestinal disease.
These objectives will be pursued by utilizing patient-derived biopsies as well as novel mouse models to manipulate EMT in the intestinal epithelium. Comprehensive analysis, including RNA-sequencing and multispectral imaging, of the involved cellular and microenvironmental components (epithelial barrier, immune cells, fibroblasts) will be performed in acute and chronic colitis settings to mechanistically configure EMT as an epithelial injury response and a major functional driver in the pathogenesis of IBD.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
20090 Pieve Emanuele
Italie