Bacterial exosomes for therapeutic immunomodulation of autoimmune kidney disease

Exosomes are secreted by most cells and have untapped immunomodulatory activity. Cell therapy can be toxic and generate a lower degree of therapeutic efficacy. Exosomes due to their small size offer an alternative with less associated toxicity. Harnessing exosomes to deliver treatment has great potential as a new therapeutic. In particular bacterial Exosomes from gut bacteria can be used to modulate NFkB a key transcription factor in initiating inflammatory pathways. It is becoming increasingly apparent that host-gut interactions have a critical role in maintaining self tolerance. Exosomes from bacteria can promote immune tolerance, in particular secretion of IL-10 from PBMCs, inducing T regulatory cells, and tolerogenic dendritic cells. This project aims to use bacterial Exosomes to induce tolerance in animal models of ANCA associated vasculitis, anti GBM disease and Lupus nephritis all diseases with suboptimal treatment options. Aim 1: To identify gut bacteria that produce immunomodulatory factors, using co-cultures. Aim 2: Use immunomodulatory Exosomes from bacteria to induce tolerance in autoimmune kidney diseases: A. ANCA vasculitis B. anti GBM disease C. Lupus Nephritis