Dynamic compartmentalization of myeloid cell responses in neuroinflammation

PD.Dr. Chotima Böttcher

• B05

Project Summary

Neuroinflammation is a common feature of autoimmune CNS diseases such as multiple sclerosis (MS), in which the pathologies are associated with local inflammation, microglial activation, and infiltration of peripheral immune cells. High dimensional immune profiling using mass cytometry revealed less inflammatory phenotypes of myeloid cells in the peripheral blood of patients with early MS, compared with those of patients with Crohn’s disease. Our findings suggest that myeloid cell responses in early MS might be related to the more compartmentalized inflammation in the CNS. Thus, immune profiling of more diverse myeloid cell types including brain microglia, choroid plexus macrophage and circulating myeloid cells in the cerebrospinal fluid is required for better understanding dynamic compartmentalization of these cells in early MS, as well as in the progressive stages. To do so, firstly, we shall comparatively characterize the distinct phenotypes of myeloid cells in the peripheral blood, cerebrospinal fluid, choroid plexus and the brain of MS patients/donors using mass cytometry. Secondly, identified markers and potential signalling pathways obtained from the first study will be validated on brain sections by the use of imaging mass cytometry. Finally, we will assess dynamic cell signalling of myeloid cells from different compartments using a combination of deep protein profiling and co- and/or multiple-primary cell culture approaches. In whole we aim to characterize neuroinflammation-associated phenotypic transmission of myeloid cells and how these cells are involved in CNS homeostasis.