Sensing the microenvironment of the central nervous system: immune cells in the central nervous system and their pharmacological manipulation

Abstract

Immune responses are highly regulated in all organs and severely restricted in certain tissues within the central nervous system (CNS). This phenomenon, called 'immune privilege', has been linked to the existence of multiple anatomical and physiological protective mechanisms. The finely balanced anti-inflammatory microenvironment within the CNS contributes to the immune privilege status of this tissue. The regulation of this compartment changes under pathological conditions when pro-inflammatory mediators might dominate. The past few years brought a wealth of novel information fostering our understanding of how CNS resident cells regulate the functions of immune cells, particularly helper T lymphocytes (Ths) and dendritic cells (DCs). These two cell types play a crucial role in the initiation and maintenance of neuroinflammatory diseases. The change from anti-inflammatory to pro-inflammatory microenvironment in the inflamed CNS affects Th and DC accumulation and function in the nervous tissue. A new era of DC-targeted therapies has begun, with the possibility of designing novel immunomodulatory therapies to intervene with neuroinflammation in a wide range of neurological diseases.

Figure 1

Some of the critical physiological, anatomical features and molecules that contribute to the regulation of immune responses in the non-inflamed CNS.

Figure 2

Path of immune cells through the BBB and neurovascular unit in their journey into the CNS parenchyma in CNS inflammation. Cerebral microvascular endothelium, together with astrocytes, neurons, and the basement membranes of endothelial cells (EBM) or astrocytes (ABM), constitute a "neurovascular unit" that is essential for the health and function of the CNS.