Extracellular vesicles as modulators of humoral auto-immune responses: Relevance to transplantation

Abstract

Mounting evidence suggests that autoimmune humoral responses contribute both to rejection of solid organ transplants and to GVHD. Production of danger associated molecular patterns (DAMPs) at sites of tissue injury have been implicated in activation of autoimmune pathways, but the specific mechanisms triggering loss of tolerance to self and leading to production of autoantibodies remain to be fully characterized. Here, we will review recent evidence implicating the release of extracellular membrane vesicles as important regulators of auto-immune responses of importance in transplantation. We will review the impact of various types of extracellular membrane vesicles i.e. microparticles, exosomes and apoptotic bodies, on antigen presentation, B cell function and production of autoantibodies. We will also review the molecular mechanisms that control the production of extracellular membrane vesicles, with a specific emphasis on caspase-dependent pathways.