title: Unimpaired dendritic cell functions in MVP/LRP knockout mice.
abstract: Dendritic cells (DCs) act as mobile sentinels of the immune system. By stimulating T lymphocytes, DCs are pivotal for the initiation of both T- and B-cell-mediated immune responses. Recently, ribonucleoprotein particles (vaults) were found to be involved in the development and/or function of human DCs. To further investigate the role of vaults in DCs, we examined the effects of disruption of the major vault protein (MVP/LRP) on the development and antigen-presenting capacity of DCs, using our MVP/LRP knockout mouse model. Mononuclear bone marrow cells were isolated from wild-type and knockout mice and stimulated to differentiate to DCs. Like human DCs, the wild-type murine DC cultures strongly expressed MVP/LRP. Nevertheless, the MVP/LRP-deficient DCs developed normally and showed similar expression levels of several DC surface markers. No differences were observed in in vitro studies on the antigen uptake and presenting capacities of the wild-type and MVP/LRP knockout DCs. Moreover, immunization of the MVP/LRP-deficient mice with several T-cell antigens led to responses similar to those observed in the wild-type mice, indicating that the in vivo DC migration and antigen-presentation capacities are intact. Moreover, no differences were observed in the induction of the T cell-dependent humoral responses and orally induced peripheral T-cell tolerance. In conclusion, vaults are not required for primary DC functions. Their abundance in DCs may, however, still reflect basic roles in myeloid cell proliferation and DC development.
authors.affiliation: Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Marieke H
authors.initials: MH
authors.lastname: Mossink
authors.forename: Jan
authors.initials: J
authors.lastname: de Groot
authors.forename: Arend
authors.initials: A
authors.lastname: van Zon
authors.forename: Erna
authors.initials: E
authors.lastname: Fränzel-Luiten
authors.forename: Martijn
authors.initials: M
authors.lastname: Schoester
authors.forename: George L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Erik A C
authors.initials: EA
authors.lastname: Wiemer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis; D016130:Immunophenotyping; D007959:Lymphocyte Culture Test, Mixed; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000099187:Major Vault Protein
chemical_list: D007074:Immunoglobulin G; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein