P5 - The role of polysialic acid shedding for the innate immune response

Polysialic acid (polySia) emerges as a novel regulator of microglia and macrophage reactivity. We recently identified a pool of polySia on two different protein carriers, which accumulates in the Golgi compartment of microglia and macrophages and is released in response to inflammatory stimulation. Based on the observation that experimentally applied polySia inhibits and loss of polySia synthesis enhances the inflammatory response, we suggest that the shedding of polysialylated proteins provides negative feedback regulation of microglia and macrophage activation. Major open questions concern the functional relevance of the marked differences between the proposed polySia receptors in mice and man as well as the possible role of polySia shedding in the regulation of chemokine recognition. The goal of this project is to decipher mechanisms by which polySia is able to impact the activity of microglia and macrophages. This will be key for developing novel therapeutic strategies to control (neuro-) inflammation by modulation of polySia shedding as a part of the innate immune response.