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: Rachel Spiering, Bram Margry, Chantal Keijzer, Cathleen Petzold, Aad Hoek, Josée Wagenaar-Hilbers, Ruurd van der Zee, Willem van Eden, Karsten Kretschmer, Femke Broere
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 194 Issue 10 Pg. 4804-13 (May 15 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 25862815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• Vaccines

Topics

• Animals
• Arthritis, Experimental (immunology)
• Arthritis, Rheumatoid (immunology)
• Dendritic Cells (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Immune Tolerance (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Vaccines (immunology)