An ideal immune system attacks non-self (e.g. pathogens) and ignores self (host tissue).
Immune tolerance is a critical homeostatic process that involves a number of checks to purge the body of autoreactive white blood cells.
Autoimmune disease such as rheumatoid arthritis, Type I diabetes and psoriasis all result from a failure to induce immune tolerance.
In order to better our understanding of mechanisms of immune tolerance, we have been studying the role of blood and lymph - borne lipid particles in this process.
Lipid bound vesicles from dying cells as well as exosomes (nanoparticles derived from living cells) may transport self-molecules around the body to induce tolerance to self.
We have previously discovered that B cell-derived exosomes are targeted to a specific macrophage population in spleen and lymph node to induce immune tolerance.
In addition, carbohydrates (present on the vesicle surface) help guide the vesicles to macrophages in the lymph node and spleen. For this project, we will uncover the mechanisms of tolerance induction by following the fate of vesicles trapped in the spleen and lymph node.
This project will provide the first information on how surface carbohydrates affect the ability of vesicles to modulate the immune response.
In addition, B cell-derived exosomes are easily generated in vitro and represent donor-matched vesicles that could be exploited to induce tolerance in a clinical setting.