title: Thymic CCL2 influences induction of T-cell tolerance.
abstract: Thymic epithelial cells (TEC) and dendritic cells (DC) play a role in T cell development by controlling the selection of the T cell receptor repertoire. DC have been described to take up antigens in the periphery and migrate into the thymus where they mediate tolerance via deletion of autoreactive T cells, or by induction of natural regulatory T cells. Migration of DC to thymus is driven by chemokine receptors. CCL2, a major ligand for the chemokine receptor CCR2, is an inflammation-associated chemokine that induces the recruitment of immune cells in tissues. CCL2 and CCR2 are implicated in promoting experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. We here show that CCL2 is constitutively expressed by endothelial cells and TEC in the thymus. Transgenic mice overexpressing CCL2 in the thymus showed an increased number of thymic plasmacytoid DC and pronounced impairment of T cell development. Consequently, CCL2 transgenic mice were resistant to EAE. These findings demonstrate that expression of CCL2 in thymus regulates DC homeostasis and controls development of autoreactive T cells, thus preventing development of autoimmune diseases.
authors.affiliation: Institute of Molecular Medicine, Department of Neurobiology Research, University of Southern Denmark, J.B. Winsløwsvej 25, DK-5000 Odense C, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Cédile
authors.affiliation: Institute of Molecular Medicine, Department of Neurobiology Research, University of Southern Denmark, J.B. Winsløwsvej 25, DK-5000 Odense C, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Løbner
authors.affiliation: Institute of Molecular Medicine, Department of Neurobiology Research, University of Southern Denmark, J.B. Winsløwsvej 25, DK-5000 Odense C, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Toft-Hansen
authors.affiliation: Institute of Molecular Medicine, Department of Neurobiology Research, University of Southern Denmark, J.B. Winsløwsvej 25, DK-5000 Odense C, Denmark.
authors.forename: I
authors.initials: I
authors.lastname: Frank
authors.affiliation: Institute of Molecular Medicine, Department of Neurobiology Research, University of Southern Denmark, J.B. Winsløwsvej 25, DK-5000 Odense C, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Wlodarczyk
authors.affiliation: Centre d'Immunologie de Marseille-Luminy - CIML, Institut National de la Santé et de la Recherche Médicale, U1104, Centre National de la Recherche Scientifique, UMR7280 and Aix Marseille Université, UM2, F-13009 Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Irla
authors.affiliation: Institute of Molecular Medicine, Department of Neurobiology Research, University of Southern Denmark, J.B. Winsløwsvej 25, DK-5000 Odense C, Denmark. Electronic address: towens@health.sdu.dk.
authors.forename: T
authors.initials: T
authors.lastname: Owens
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology
chemical_list: C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2
keywords: CCL2; EAE; Plasmacytoid dendritic cells; Tolerance