Conclusions

It is now well established that immune cells reach the CNS via the bloodstream and can enter the CNS during both health and disease. Traffic signals guiding immune cells across the BBB seem to be different under normal physiological and pathological conditions and might even vary during different stages of inflammation, depending on the inflammatory stimulus and the CNS site involved. Present observations suggest that there are differences in endothelial traffic signals utilized within meningeal versus parenchymal or CNS white matter versus grey matter, or spinal cord versus brain microvessels, which could well result in the recruitment of different leukocyte subpopulations into different sites within the CNS. The immune privilege of the CNS might serve the purpose to regionally regulate the expression of the respective traffic signals to avoid the entry of potentially harmful immune cells such as neutrophils or macrophages into the CNS parenchyma. Continued research will be essential to precisely understand the role of adhesion and signalling molecules involved in the multi-step recruitment of leukocytes across the BBB during health and disease. Once we understand the molecular codes used by the different leukocyte subpopulations (CD4+ T cells, CD8+ T cells, B cells, monocytes and dendritic cells) to breach the BBB, specific anti-inflammatory therapies might be developed that selectively target the migration of pathogenic leukocyte subpopulation across the BBB, while leaving CNS immunosurveillance untouched. Vice versa, this knowledge might as well be used to direct genetically modified beneficial cells such as killer cells or stem cells across the BBB into the CNS to kill tumors efficiently or to repair damaged tissue.

Acknowledgement I owe great thanks to Urban Deutsch for critically discussing this chapter.

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