Purinergic receptors and pannexin channels in the activation of innate immune cells of the choroid plexus

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The immune response is an orchestrated biochemical cascade that initiates systemic responses to invasive organisms or molecules. Traditionally, the brain has been considered to be an immune privileged organ, remaining isolated from the circulation because of a substantial blood brain barrier. However, at the level of the brain ventricles, the choroid plexus contains blood vessels that are highly permeable to molecules and cells. It is not known how an immune privileged barrier is generated at the choroid plexus, but it appears to involve a unique class of macrophage-like cells, the epiplexus or Kolmer cells. This proposed research program aims to understand the cellular physiology of epiplexus cells in the context of the systemic immune system. In three specific Objectives, I will investigate the ion channels and receptors that are responsible for epiplexus cell activation, determine how epiplexus cells communicate with the epithelial cells of the choroid plexus, and investigate how systemic immune challenges, given in vivo, alter acute responses of epiplexus cells. The research program will build upon the lab's expertise and world leadership in the area of pannexin-1 ion channel biology. Our approach is unique and innovative, providing exciting opportunities for the training and development of highly qualified personnel. The work here will dramatically increase our understanding of how immune challenges contribute to brain barriers and identify the role of specific cell types and ion channels in this fundamental physiological mechanism.