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.