Choroid plexus as a mediator of CNS inflammation in multiple sclerosis

The pathophysiology of multiple sclerosis (MS) remains poorly understood despite decades of tremendous research efforts. Advances in neuroradiography coupled with availability of unbiased approaches including spatial transcriptomics, proteomics, metabolomics, and lipidomics that are compatible with brain and fluid specimens from patients raise hope that discovery of novel disease drivers is on the horizon. Once thought to be little more than salty bathwater, our modern understanding of cerebrospinal fluid (CSF) suggests the CSF as a compelling, critical regulator of brain function in health and disease. Recent studies in the field have reinvigorated interest in CSF as a medium to better understand MS and to deliver disease-modifying therapies. In turn, the choroid plexus, an epithelial tissue located within each brain ventricle that regulates CSF and forms a key blood-CSF barrier, is uniquely positioned to orchestrate neuroinflammation associated with MS. In this perspective review, we will discuss what is known about the choroid plexus as a conductor of immune responses and how it may propagate neuroinflammation associated with MS via the CSF.