Define pathophysiological and immunoregulatory mechanisms involved in the initiation and the progression of inflammatory diseases and fibrosis.
Leader: Gilles Chiocchia, Inserm U1173, Partner 8
This workpackage is by essence the first step to a better understanding of specific and common pathophysiologic principles underlying inflammatory diseases. This is why, all partners are involved in this WP .The aim of our work is to shed light on both the mechanisms involved in disease initiation and progression with a particular attention on fibrosis development. In this line, our strategy follows two main axes of research:
1. Identification and analysis of predisposing genetic factors for inflammatory diseases. On this point groups of the Labex already identified several predisposing locus in different inflammatory diseases.
As previously planned, identified candidate molecules have started to be or will be investigated mechanistically using either already established disease models, or by generating new appropriate transgenic animal models carrying either deficiencies or relevant mutants of the respective molecules. Each identified locus or molecule in one of the targeted diseases will also be studied for possible impact on other inflammatory diseases investigated within the network allowing to define both common and specific factors. Thus each benchmark result from one group will allow synergizing studies through the Labex partners.
2. Identification and study of innate immune effectors cells, receptors, inflammatory mediators and signaling effectors in the development and progression of inflammatory diseases.
This axis aims to define the pathophysiologic crosstalk between infiltrating cells, their microenvironment and released inflammatory mediators that promote disease initiation and that are involved in tissue remodeling, epithelial alterations, fibroblast proliferation and extracellular matrix accumulation in various inflammatory diseases. The various teams of INFLAMEX network have all a great expertise in such approach mening that numerous results have already been obtained by several partners particularly regarding the role of immune cells, molecular regulators and new targets. These results lay the ground to develop new animal models, testing the validity of potential new markers.
This WP will thus allow the definition of common or specific cellular and molecular pathways in the various systems that are responsible for the genesis and the development of inflammatory diseases and define possible new effector pathways and analytical tools for the study of inflammatory diseases.