Exosomes act as endogenous messengers transferring signals between tissue cells and the immune system

Exosomes are small membrane micro vesicles released by cells, and present in almost all biological fluids. They are believed to play an important role in intercellular communication and immune regulation. Recently, an increase in exosomal albumin mRNA has been observed in drug-treated hepatocytes. In recent studies we have identified two distinct patterns of cross-talk between tissue cells and dendritic cells: 1, stress-induced signalling; and 2, a non-stress related signalling, with both pathways resulting in unique dendritic cell cytokine profiles. Mass spectrometry has also identified over 500 hepatocyte-derived proteins within exosomes, some of which are modified with drugs. Thus, selective packaging of tissue-derived exosomes may be an important factor in regulating drug-specific immune responses. The hypothesis of the project is that drug exposure determines the selective packaging of hepatocyte and keratinocyte-derived exosomes, which regulates the adaptive immune response through dendritic cell signalling.