It is now accepted that blood-derived immune cells and microbial products shape brain development, function, aging, and disease, yet the presence of such factors in the brain territory is limited. So how can they exert their powerful effect on the nervous system from afar?

The choroid plexus (CP) epithelium is a monolayer barrier tissue, which on the side facing the blood can sense such peripheral factors, and on the side facing the brain, produces the cerebrospinal fluid (CSF)–a liquid carrying nutrients and signaling molecules, which contacts nearly all brain cells, and ensures brain homeostasis. We study how the peripheral immune and microbial factors may shape brain function indirectly, via regulation of the CSF properties at the CP epithelium in brain development, normal physiological function, aging, and disease. Our goal is to identify fundamental principles of physiological brain regulation by the peripheral factors to pave the way for future investigation of the gut-blood-CP-brain communication circuit in neurological disease.