title: Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System.
abstract: Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as "assistants" in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several 'checkpoints' from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS) diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets.
authors.affiliation: Discipline of Medical Imaging & Radiation Sciences, Faculty of Health Sciences, The University of Sydney, Sydney, NSW 2141, Australia. meredith.harrisonbrown@sydney.edu.au.|Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234, Australia. meredith.harrisonbrown@sydney.edu.au.
authors.forename: Meredith
authors.initials: M
authors.lastname: Harrison-Brown
authors.affiliation: Discipline of Medical Imaging & Radiation Sciences, Faculty of Health Sciences, The University of Sydney, Sydney, NSW 2141, Australia. gdl@ansto.gov.au.|Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234, Australia. gdl@ansto.gov.au.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Liu
authors.affiliation: Discipline of Medical Imaging & Radiation Sciences, Faculty of Health Sciences, The University of Sydney, Sydney, NSW 2141, Australia. richard.banati@sydney.edu.au.|Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234, Australia. richard.banati@sydney.edu.au.|Brain and Mind Centre, The University of Sydney, Sydney, NSW 2006, Australia. richard.banati@sydney.edu.au.
authors.forename: Richard
authors.initials: R
authors.lastname: Banati
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000166:cytology*; D002465:Cell Movement; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D022423:Myeloid Cells / Q000166:cytology*; D057170:Translational Research, Biomedical
keywords: brain; microglia; myeloid cell; transplantation