title: Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance.
abstract: Central tolerance can be mediated by peripheral dendritic cells (DCs) that transport innocuous antigens (Ags) to the thymus for presentation to developing T cells, but the responsible DC subsets remained poorly defined. Immature plasmacytoid DCs (pDCs) express CCR9, a chemokine receptor involved in migration of T cell precursors to the thymus. We show here that CCR9 mediated efficient thymic entry of endogenous or i.v. transfused pDCs. pDCs activated by Toll-like receptor (TLR) ligands downregulated CCR9 and lost their ability to home to the thymus. Moreover, endogenous pDCs took up subcutaneously injected fluorescent Ag and, in the absence of TLR signals, transported Ag to the thymus in a CCR9-dependent fashion. Injected, Ag-loaded pDCs effectively deleted Ag-specific thymocytes, and this thymic clonal deletion required CCR9-mediated homing and was prevented by infectious signals. Thus, peripheral pDCs can contribute to immune tolerance through CCR9-dependent transport of peripheral Ags and subsequent deletion of Ag-reactive thymocytes.
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. hadeiba@stanford.edu
authors.forename: Husein
authors.initials: H
authors.lastname: Hadeiba
authors.forename: Katharina
authors.initials: K
authors.lastname: Lahl
authors.forename: Abdolhossein
authors.initials: A
authors.lastname: Edalati
authors.forename: Cecilia
authors.initials: C
authors.lastname: Oderup
authors.forename: Aida
authors.initials: A
authors.lastname: Habtezion
authors.forename: Russell
authors.initials: R
authors.lastname: Pachynski
authors.forename: Linh
authors.initials: L
authors.lastname: Nguyen
authors.forename: Asma
authors.initials: A
authors.lastname: Ghodsi
authors.forename: Sarah
authors.initials: S
authors.lastname: Adler
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D001693:Biological Transport, Active; D017637:Clonal Deletion / Q000276:immunology; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054388:Receptors, CCR / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D001324:Autoantigens; C119309:CC chemokine receptor 9; D054388:Receptors, CCR; D051193:Toll-Like Receptors