Simone Brioschi

During my postdoc I conducted a seminal study describing composition and origin of meningeal B cells in health and aging. This research showed that skull-derived B cells infiltrate the meninges at initial stages of their development (pro-B and pre-B cells) and locally accomplish their differentiation process. By contrast, blood-derived age-associated B cells (ABCs) accumulate in the mouse meninges during aging. We proposed that meningeal adaptive immunity is tailored to the local antigen repertoire to maintain immune privilege within the CNS. As a future study, I propose to investigate the composition and clonality of meningeal B cells in models of autoimmunity, like Lupus. Alongside, I generated a novel Cre line targeting microglia and BAMs specifically after the infiltration of the brain rudiment. I used this tool to delete the transcription factor SMAD4 in microglia and BAMs during early stages of embryonic brain development. Deletion of SMAD4 impaired microglia specification, producing broad transcriptomic changes and epigenetic remodeling. By contrast, BAM specification program was unaffected. Furthermore, mice with SMAD4-deficient microglia exhibited impaired learning and memory skills, indicating that a physiological microglia maturation during embryonic development is crucial for brain functions. I am currently investigating the role of PU.1 in microglia during amyloid pathology.