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The movers and shapers in immune privilege of the CNS

Abstract

Discoveries leading to an improved understanding of immune surveillance of the central nervous system (CNS) have repeatedly provoked dismissal of the existence of immune privilege of the CNS. Recent rediscoveries of lymphatic vessels within the dura mater surrounding the brain, made possible by modern live-cell imaging technologies, have revived this discussion. This review emphasizes the fact that understanding immune privilege of the CNS requires intimate knowledge of its unique anatomy. Endothelial, epithelial and glial brain barriers establish compartments in the CNS that differ strikingly with regard to their accessibility to immune-cell subsets. There is a unique system of lymphatic drainage from the CNS to the peripheral lymph nodes. We summarize current knowledge on the cellular and molecular mechanisms involved in immune-cell trafficking and lymphatic drainage from the CNS, and we take into account differences in rodent and human CNS anatomy.

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Figure 1: The acellular and cellular brain barriers.

Debbie Maizels/Springer Nature

Figure 2: Lymphatic drainage of the CNS in humans and in rodents.

Debbie Maizels/Springer Nature

Figure 3: Efferent immune pathways to the CNS.

Debbie Maizels/Springer Nature

Figure 4: Intravital fluorescence videomicroscopy of mouse and human CNS vasculature.

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Acknowledgements

B.E. is supported by the Swiss National Science Foundation (grants 154483, 154483 and 170131), the Swiss Multiple Sclerosis Society, the Novartis Foundation for Medical-Biological Research, EU FP7 ITN nEUROinflammation (607962), EU Horizon 2020 ITN BtRAIN (675619) and the EU/Eureka-funded Eurostars Siagen-MS (9059).

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Engelhardt, B., Vajkoczy, P. & Weller, R. The movers and shapers in immune privilege of the CNS. Nat Immunol 18, 123–131 (2017). https://doi.org/10.1038/ni.3666

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