Abstract
The CNS is protected by the immune system, including cells that reside directly within the CNS and help to ensure proper neural function, as well as cells that traffic into the CNS with disease. The CNS-resident immune system is comprised mainly of innate immune cells and operates under homeostatic conditions. These myeloid cells in the CNS parenchyma and at CNS–periphery interfaces are highly specialized but also extremely plastic cells that immediately react to any changes in CNS homeostasis and become reactive in the context of neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease. However, when the blood–brain barrier is impaired during CNS diseases such as multiple sclerosis or altered with cerebral ischemia, peripheral adaptive and innate immune cells, including monocytes, neutrophils, T cells and B cells, can enter the CNS, where they execute distinct cell-mediated effects. On the basis of these observations, we assess strategies for targeting peripheral immune cells to reduce CNS disease burden.
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Acknowledgements
We thank Dr. F. Fernández-Klett and D. Erny for the artwork. M.P. and J.P. are coordinators of the DFG-funded collaborative research center SFB/TRR167 (NeuroMac). In addition, M.P. is supported by the BMBF-funded competence network of multiple sclerosis (KKNMS) and the DFG (SFB 992, SFB 1160, Reinhart Koeselleck Grant). J.P. receives additional funding from the DFG (NeuroCure Cluster of Excellence, SFB TRR43), the BIH (CRG Proteostasis) and the BMBF (AERIAL).
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Prinz, M., Priller, J. The role of peripheral immune cells in the CNS in steady state and disease. Nat Neurosci 20, 136–144 (2017). https://doi.org/10.1038/nn.4475
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DOI: https://doi.org/10.1038/nn.4475
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