title: Pivotal Role for CD16+ Monocytes in Immune Surveillance of the Central Nervous System.
abstract: Monocytes represent a heterogeneous population of primary immune effector cells. At least three different subsets can be distinguished based on expression of the low-affinity FcγRIII: CD14(++)CD16 -: classical monocytes, CD14(++)CD16(+) intermediate monocytes, and CD14(+)CD16 ++: non-classical monocytes. Whereas CD16 -: classical monocytes are considered key players in multiple sclerosis (MS), little is known on CD16(+) monocytes and how they contribute to the disease. In this study, we examined the frequency and phenotype of monocyte subpopulations in peripheral blood, cerebrospinal fluid (CSF), and brain biopsy material derived from MS patients and controls. Furthermore, we addressed a possible monocyte dysfunction in MS and analyzed migratory properties of monocyte subsets using human brain microvascular endothelial cells. Our ex vivo studies demonstrated that CD16(+) monocyte subpopulations are functional but numerically reduced in the peripheral blood of MS patients. CD16(+) monocytes with an intermediate-like phenotype were found to be enriched in CSF and dominated the CSF monocyte population under noninflammatory conditions. In contrast, an inversed CD16(+) to CD16 -: CSF monocyte ratio was observed in MS patients with relapsing-remitting disease. Newly infiltrating, hematogenous CD16(+) monocytes were detected in a perivascular location within active MS lesions, and CD16(+) monocytes facilitated CD4(+) T cell trafficking in a blood -: brain barrier model. Our findings support an important role of CD16(+) monocytes in the steady-state immune surveillance of the CNS and suggest that CD16(+) monocytes shift to sites of inflammation and contribute to the breakdown of the blood-brain barrier in CNS autoimmune diseases.
authors.affiliation: Department of Neurology, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; Anne.Waschbisch@uk-erlangen.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Waschbisch
authors.affiliation: Department of Neurology, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany;
authors.forename: Sina
authors.initials: S
authors.lastname: Schröder
authors.affiliation: Department of Neurology, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany;
authors.forename: Dana
authors.identifier: http://orcid.org/0000-0002-0521-0029
authors.initials: D
authors.lastname: Schraudner
authors.affiliation: Department of Neurology, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany;
authors.forename: Laura
authors.identifier: http://orcid.org/0000-0003-1054-1671
authors.initials: L
authors.lastname: Sammet
authors.affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, NY 10065; and.
authors.forename: Babette
authors.identifier: http://orcid.org/0000-0003-4129-9283
authors.initials: B
authors.lastname: Weksler
authors.affiliation: Department of Neurology, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany;
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.affiliation: Department of Neuropathology, University Medical Center, Georg August University Göttingen, 37075 Göttingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pfeifenbring
authors.affiliation: Department of Neuropathology, University Medical Center, Georg August University Göttingen, 37075 Göttingen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
authors.affiliation: Department of Neurology, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwab
authors.affiliation: Department of Neurology, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany;
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
mesh_terms: D000328:Adult; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology; D001812:Blood-Brain Barrier / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement; D002490:Central Nervous System / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000166:cytology; D042783:Endothelial Cells; D005260:Female; D006801:Humans; D007157:Immunologic Surveillance; D007249:Inflammation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000502:physiology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology; D010641:Phenotype; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D017452:Receptors, IgG