title: CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation.
abstract: Perivascular macrophages (PVM) constitute a subpopulation of resident macrophages in the central nervous system (CNS) that by virtue of their strategic location at the blood-brain barrier potentially lend themselves to a variety of important functions in both health and disease. Functional evidence suggests that PVM play a supportive role during experimental autoimmune encephalomyelitis in rodents. However, the function of PVM in the human CNS remains poorly characterized. We first set out to investigate the validity of the antibody EDhu1, which recognizes human CD163, to specifically identify human PVM. Second, we wanted to gain insight into the function of PVM in antigen recognition and presentation and therefore we studied the expression of DC-SIGN, mannose receptor, MHC class II, and several costimulatory molecules by PVM in the normal and inflamed human CNS (multiple sclerosis (MS) brain lesions). Conventional immunohistochemistry and double-labeled immunofluorescence techniques were used. We show that CD163 specifically reveals PVM in the normal human CNS. In MS lesions, CD163 staining reveals expression on foamy macrophages and microglia, besides an upregulation of the amount of PVM stained. In contrast, mannose receptor expression is restricted to PVM in both normal and inflamed brain tissue. Furthermore, we show that a subpopulation of PVM in the human brain express several molecules involved in antigen recognition, presentation, and costimulation. Therefore PVM, which occupy a strategic location at the BBB, are equipped to recognize antigen and present it to T cells, supporting a role in the regulation of perivascular inflammation in the human CNS.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, the Netherlands. bo.fabriek@vumc.nl
authors.forename: Babs O
authors.initials: BO
authors.lastname: Fabriek
authors.forename: Elise S
authors.initials: ES
authors.lastname: Van Haastert
authors.forename: Ian
authors.initials: I
authors.lastname: Galea
authors.forename: Machteld M J
authors.initials: MM
authors.lastname: Polfliet
authors.forename: Ed D
authors.initials: ED
authors.lastname: Döpp
authors.forename: Michel M
authors.initials: MM
authors.lastname: Van Den Heuvel
authors.forename: Timo K
authors.initials: TK
authors.lastname: Van Den Berg
authors.forename: Corline J A
authors.initials: CJ
authors.lastname: De Groot
authors.forename: Paul
authors.initials: P
authors.lastname: Van Der Valk
authors.forename: Christine D
authors.initials: CD
authors.lastname: Dijkstra
mesh_terms: D000368:Aged; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D001812:Blood-Brain Barrier / Q000166:cytology / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002536:Cerebral Arteries / Q000166:cytology / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D008833:Microcirculation / Q000166:cytology / Q000276:immunology; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D000098902:CD163 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin