Neuroimmune communication contributes to both baseline and adaptive physiological functions, as well as disease states. The vascular blood–brain barrier (BBB) and associated cells of the neurovascular unit (NVU) serve as an important interface for immune communication between the brain and periphery through the blood. Immune functions and interactions of the BBB and NVU in this context can be categorized into at least five neuroimmune axes, which include (1) immune modulation of BBB impermeability, (2) immune regulation of BBB transporters, secretions, and other functions, (3) BBB uptake and transport of immunoactive substances, (4) immune cell trafficking, and (5) BBB secretions of immunoactive substances. These axes may act separately or in concert to mediate various aspects of immune signaling at the BBB. Much of what we understand about immune axes has been from work conducted using in vitro BBB models, and recent advances in BBB and NVU modeling highlight the potential of these newer models for improving our understanding of how the brain and immune system communicate. In this review, we discuss how conventional in vitro models of the BBB have improved our understanding of the 5 neuroimmune axes. We further evaluate the existing literature on neuroimmune functions of novel in vitro BBB models, such as those derived from human induced pluripotent stem cells (iPSCs) and discuss their utility in evaluating aspects of neuroimmune communication.

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神经免疫通讯中血脑屏障和界面功能的体外建模

神经免疫通信有助于基线和适应性生理功能以及疾病状态。血管血脑屏障 (BBB) 和神经血管单元 (NVU) 的相关细胞是大脑和外周通过血液进行免疫通讯的重要界面。在这种情况下，BBB 和 NVU 的免疫功能和相互作用可分为至少五个神经免疫轴，包括 (1) BBB 不渗透性的免疫调节，(2) BBB 转运蛋白、分泌物和其他功能的免疫调节，(3) ) 免疫活性物质的 BBB 摄取和运输，(4) 免疫细胞运输，和 (5) 免疫活性物质的 BBB 分泌。这些轴可以单独或协同作用以介导 BBB 免疫信号的各个方面。我们对免疫轴的了解大部分来自使用体外 BBB 模型进行的工作，BBB 和 NVU 建模的最新进展突出了这些新模型在提高我们对大脑和免疫系统如何交流的理解方面的潜力。在这篇综述中，我们讨论了传统的 BBB 体外模型如何提高了我们对 5 个神经免疫轴的理解。我们进一步评估了关于新型体外 BBB 模型神经免疫功能的现有文献，例如源自人类诱导多能干细胞 (iPSC) 的模型，并讨论了它们在评估神经免疫通讯方面的效用。BBB 和 NVU 建模的最新进展凸显了这些新模型在提高我们对大脑和免疫系统如何交流的理解方面的潜力。在这篇综述中，我们讨论了传统的 BBB 体外模型如何提高了我们对 5 个神经免疫轴的理解。我们进一步评估了关于新型体外 BBB 模型神经免疫功能的现有文献，例如源自人类诱导多能干细胞 (iPSC) 的模型，并讨论了它们在评估神经免疫通讯方面的效用。BBB 和 NVU 建模的最新进展凸显了这些新模型在提高我们对大脑和免疫系统如何交流的理解方面的潜力。在这篇综述中，我们讨论了传统的 BBB 体外模型如何提高了我们对 5 个神经免疫轴的理解。我们进一步评估了关于新型体外 BBB 模型神经免疫功能的现有文献，例如源自人类诱导多能干细胞 (iPSC) 的模型，并讨论了它们在评估神经免疫通讯方面的效用。