For decades, it was commonly accepted that the brain is secluded from peripheral immune activity and is self-sufficient for its maintenance and repair. This simplistic perception was based on the presence of resident immune cells, the microglia, and barrier systems within the brain, and the assumption that the central nervous system (CNS) lacks lymphatic drainage. This view was revised with the discoveries that higher functions of the CNS, homeostasis and repair are supported by peripheral innate and adaptive immune cells. The findings of bone marrow-derived immune cells in specialized niches, and the renewed observation that a lymphatic drainage system exists within the brain, further contributed to this revised model. In this Review, we describe the immune niches within the brain, the contribution of professional immune cells to brain functions, the bidirectional relationships between the CNS and the immune system and the relevance of immune components to brain aging and neurodegenerative diseases.
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The Schwartz research group is supported by an Advanced European Research Council grant (no. 7417), an Israel Science Foundation (ISF) research grant (no. 991/16) and an ISF Legacy Heritage Bio-Medical Science Partnership research grant (no. 1354/15). We thank the Thompson Foundation for generous support of Alzheimer’s disease research, and S. Schwarzbaum for editing the manuscript.
M.S. is a consultant for ImmunoBrain Checkpoint. All other authors have no competing interests.
Peer review information Nature Immunology thanks the anonymous reviewers for their contribution to the peer review of this work. Ioana Visan was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.
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Croese, T., Castellani, G. & Schwartz, M. Immune cell compartmentalization for brain surveillance and protection. Nat Immunol 22, 1083–1092 (2021). https://doi.org/10.1038/s41590-021-00994-2