Understanding the role of the arachnoid barrier in neuroimmune communication

For decades the immune system and the nervous system were thought to be completely cut off from one another. This was thought to be the explanation for immune privilege, whereby the immune system tolerates foreign antigens present in the CNS. However, research in the last decade has shown that neuroimmune communication is essential for protection, healing, and function of the central nervous system (CNS). Instead of being isolated, immune responses in the CNS are compartmentalised by a series of physical barriers. The best known is the blood-brain barrier which is present in the brain's blood vessels. However, there are additional barriers at other brain borders that contact the cerebrospinal fluid (CSF). One of these barriers, the arachnoid barrier, is found in the meninges, and segregates the immune-rich outer layer of the meninges (the dura mater), from the CSF below it. We hypothesise that the arachnoid barrier is important to restrict the availability of CNS antigens in the dura mater, restricting immune responses to homeostatic peptides that promote tolerance. In this way, we propose that the arachnoid barrier is important to protect the brain from collateral damage from an overactive immune system. We will test the function of the arachnoid barrier in neuroimmune communication by using genetic models to break it. We will develop an inducible model of arachnoid barrier leakage, then study how this alters immune responses to the CNS, and determine if this occurs in inflammation to trigger autoimmune responses.