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

免疫反应是一种精心安排的生物化学级联反应，启动对入侵生物或分子的系统性反应。传统上，大脑被认为是一个免疫特权器官，由于大量的血脑屏障，它与血液循环隔绝。然而，在脑室的水平上，脉络丛包含对分子和细胞具有高度渗透性的血管。目前尚不清楚免疫特权屏障是如何在脉络丛产生的，但它似乎涉及一种独特的巨噬细胞样细胞，即上神经丛或Kolmer细胞。这项拟议的研究计划旨在了解系统免疫系统背景下的丛上细胞的细胞生理学。在三个特定的目标中，我将研究负责神经丛上皮细胞激活的离子通道和受体，确定神经丛细胞如何与脉络丛上皮细胞通信，并研究体内给予的全身免疫挑战如何改变神经丛上细胞的急性反应。该研究计划将建立在该实验室在Pannexin-1离子通道生物学领域的专业知识和世界领先地位的基础上。我们的方法是独特和创新的，为高素质人才的培训和发展提供了令人兴奋的机会。这项工作将极大地提高我们对免疫挑战如何影响脑屏障的理解，并确定特定细胞类型和离子通道在这一基本生理机制中的作用。

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.