The Choroid Plexus is a Niche that Regulates Adaptive Immunity Within the Central Nervous System: Implications to Neuroinflammatory Diseases

The choroid plexus (CP) compartment is located in the brain ventricles and comprises fenestrated vasculature permeable for blood-born inflammatory mediators. The CP responds rapidly to peripheral inflammation by elevating the expression of numerous immune mediators which impact neuroinflammation. Whereas T cells - key components of adaptive immunity - were shown to be recruited to the CP in several neurodegenerative diseases such as amyotrophic lateral sclerosis, and stroke, the unique role of the CP, compared to other blood-brain barriers, in T cell-mediated brain inflammation is not fully explored. Following to our previous findings which demonstrate that T cells harbor in the CP as an immunological niche that allows their stimulation and proliferation, we aimed to determine the conditions which promote the migration of circulating T cells to the CP and their subsequent activation by CP myeloid cells. We show that neither increased chemokine expression in the CP nor the presence of cognate T-cell antigens, were sufficient to recruit T cells from the periphery into the CP stroma. However, polyclonal proliferating T cells, which were recruited into the CP from the ventricle, facilitated a marked antigen-dependent T-cell entry from the circulation. Together, our data suggest that recruitment of brain antigen-specific T cells into the CP is tightly regulated and involves molecular cues induced in the CP following activation of cerebrospinal fluid (CSF)- or CP- resident T cells. Such process of T-cell recruitment into the CP may orchestrate adaptive immunity in the central nervous system and thus targeted therapeutically in various brain pathologies.