Pathomechanisms (PI JL Guéant)

We will address an interdependent network of mechanisms in the three disease groups from environment to cellular consequences. The first level of the network is the environment and multi-organ system, for which we will focus our interest on dietary methyl donors and dysbiosis as master components of environmental factors acting on metabolism epigenomic, energy metabolism and cellular stress. Barriers (intestinal and gastric epithelium, stellate cells, synoviocytes) will be considered as a function of their pathological duality, protection of organs and tissues from environment and targets of cellular and tissue stress. Epigenomic plays a central role through its influence on energy metabolism, reticulum stress and innate immunity. Remodeling will be regarded as a result of cellular stress, inflammation and extra-cellular matrix.