title: DEC205+ Dendritic Cell-Targeted Tolerogenic Vaccination Promotes Immune Tolerance in Experimental Autoimmune Arthritis.
abstract: Previous studies in mouse models of autoimmune diabetes and encephalomyelitis have indicated that the selective delivery of self-antigen to the endocytic receptor DEC205 on steady-state dendritic cells (DCs) may represent a suitable approach to induce Ag-specific immune tolerance. In this study, we aimed to examine whether DEC205(+) DC targeting of a single immunodominant peptide derived from human cartilage proteoglycan (PG) can promote immune tolerance in PG-induced arthritis (PGIA). Besides disease induction by immunization with whole PG protein with a high degree of antigenic complexity, PGIA substantially differs from previously studied autoimmune models not only in the target tissue of autoimmune destruction but also in the nature of pathogenic immune effector cells. Our results show that DEC205(+) DC targeting of the PG peptide 70-84 is sufficient to efficiently protect against PGIA development. Complementary mechanistic studies support a model in which DEC205(+) DC targeting leads to insufficient germinal center B cell support by PG-specific follicular helper T cells. Consequently, impaired germinal center formation results in lower Ab titers, severely compromising the development of PGIA. Overall, this study further corroborates the potential of prospective tolerogenic DEC205(+) DC vaccination to interfere with autoimmune diseases, such as rheumatoid arthritis.
authors: Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands;
authors: Rachel
authors: R
authors: Spiering
authors: Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands;
authors: Bram
authors: B
authors: Margry
authors: Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands;
authors: Chantal
authors: C
authors: Keijzer
authors: Department of Molecular and Cellular Immunology/Immune Regulation, German Research Foundation-Center for Regenerative Therapies Dresden, Dresden University of Technology, 01307 Dresden, Germany; and.
authors: Cathleen
authors: C
authors: Petzold
authors: Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands;
authors: Aad
authors: A
authors: Hoek
authors: Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands;
authors: Josée
authors: J
authors: Wagenaar-Hilbers
authors: Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands;
authors: Ruurd
authors: R
authors: van der Zee
authors: Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands;
authors: Willem
authors: W
authors: van Eden
authors: Department of Molecular and Cellular Immunology/Immune Regulation, German Research Foundation-Center for Regenerative Therapies Dresden, Dresden University of Technology, 01307 Dresden, Germany; and Paul Langerhans Institute Dresden, German Center for Diabetes Research, 01307 Dresden, Germany.
authors: Karsten
authors: K
authors: Kretschmer
authors: Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands; f.broere@uu.nl.
authors: Femke
authors: F
authors: Broere
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D014612:Vaccines / Q000276:immunology*
chemical_list: D014612:Vaccines