Abstract

Microglia, as tissue resident macrophages of the CNS , play important roles in development and maintaining homeostasis. Heterogeneity of these autonomously self-renewing myeloid cells reflects plasticity in response to microenvironmental changes which include aging, inflammation, degeneration and injury. Nevertheless transcriptomic signatures from a number of studies show similar overlapping microglial gene expression patterns in homeostasis as well as in disease or injury, and a core signature for a unique subset can be identified. Tracking this subset based on CD11c expression revealed homeostatic and anti-inflammatory characteristics which could be exploited for amelioration of EAE in adult mice by expansion of this subset by CSF1R ligands. Myelination in early postnatal CNS is promoted by IGF1 deriving from CD11c+ microglia and data will be presented showing that transfer of neonatal microglia to adult mice suppressed EAE . In a mouse model for NMOSD induced by transfer of patient-derived IgG, microglia (including the CD11c+ subset) showed a strong type I IFN transcriptomic footprint, and consistent with NMOSD being IFN I -dependent, microglial depletion abrogated both IFN I -induced gene expression as well as prevented induction of NMOSD pathology. Taken together, these findings provide a glimpse into the context-dependent complexity of microglial modulation of CNS homeostasis.