P05 - Interaction

Neuronal control of phagocytes during CNS inflammation

The regulation of immune responses in the nervous system determines the course of neurological conditions with primary CNS inflammation, such as the common autoimmune disease multiple sclerosis (MS) but also of conditions, in which inflammation arises secondary to traumatic injuries to the brain and spinal cord.

Classically we focus on how inflammatory reactions affect the CNS, but it is getting increasingly clear that resident cells including neurons also play an active role in shaping immune reactions in the CNS. Indeed, in our preliminary work we can show that macrophages adapt their phenotypes in inflammatory lesions in response to CNS derived signals and that the neuronal guidance molecule netrin is a key component of this neuronal instruction of CNS inflammation. In this project we now want to provide a refined molecular understanding of the underlying signalling pathways that mediate neuronal control of phagocyte actions-

In this project we will study autoimmune and traumatic conditions of the CNS using both disease models and tissue samples. By applying cutting edge molecular biology microscopy techniques we want to (i) determine the molecular and functional characterization of netrin-1 as a neuronal regulator of phagocyte actions during autoimmune and post-traumatic CNS inflammation and (ii) comprehensively dissect the neuronal regulation of phagocyte actions during autoimmune and post-traumatic CNS inflammation

By understanding the way neurons communicate with infiltrating immune cells we want to gain new mechanistic insight into the regulation of inflammatory processes in the CNS and pave the way for the identification of new targets for site- and disease-specific modulation of CNS inflammation.