title: Specialized role of migratory dendritic cells in peripheral tolerance induction.
abstract: Harnessing DCs for immunotherapies in vivo requires the elucidation of the physiological role of distinct DC populations. Migratory DCs traffic from peripheral tissues to draining lymph nodes charged with tissue self antigens. We hypothesized that these DC populations have a specialized role in the maintenance of peripheral tolerance, specifically, to generate suppressive Foxp3+ Tregs. To examine the differential capacity of migratory DCs versus blood-derived lymphoid-resident DCs for Treg generation in vivo, we targeted a self antigen, myelin oligodendrocyte glycoprotein, using antibodies against cell surface receptors differentially expressed in these DC populations. Using this approach together with mouse models that lack specific DC populations, we found that migratory DCs have a superior ability to generate Tregs in vivo, which in turn drastically improve the outcome of experimental autoimmune encephalomyelitis. These results provide a rationale for the development of novel therapies targeting migratory DCs for the treatment of autoimmune diseases.
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, New York, USA. ijuliana@rockefeller.edu.
authors.forename: Juliana
authors.initials: J
authors.lastname: Idoyaga
authors.forename: Christopher
authors.initials: C
authors.lastname: Fiorese
authors.forename: Lori
authors.initials: L
authors.lastname: Zbytnuik
authors.forename: Ashira
authors.initials: A
authors.lastname: Lubkin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Miller
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Daniel
authors.initials: D
authors.lastname: Mucida
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001324:Autoantigens; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000502:physiology; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000037:antagonists & inhibitors / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D061166:Peripheral Tolerance / Q000276:immunology* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000276:immunology; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D001324:Autoantigens; C498497:Cd207 protein, mouse; C093569:DEC-205 receptor; C526731:Dcir protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D015778:Minor Histocompatibility Antigens; C571327:Mog protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C539378:Treml4 protein, mouse