The research focus of this project area concentrates on structural analyses and characterization of CD83 related signal transduction pathways. Specific interaction partners have been identified using a Ligand-Based Receptor Capture assay, and will now be further evaluated.
In addition, the 3-demensional structure of the extracellular CD83 domain has been established up to a resolution of 1.7Å, using X-ray crystallography. To identify possible binding motifs in silico, a bioinformatic modeling study has been performed.
Using our recently generated DC specific CD83 conditional KO animals we discovered that CD83 modulates proinflammatory TLR2/4 signaling pathways, thereby potently regulating immune responses in a DC dependent manner. Regarding regulatory T cells, we reported for the first time that CD83 is absolutely essential for the resolution of inflammation, since deletion of CD83 on these cells causes a massive over activation of the immune system, with exacerbated autoimmune reactions, as observed in animal models for arthritis and inflammatory bowel disease.
In follow up studies we will now elucidate the precise underlying mechanisms and use this knowledge for the development of future therapeutic intervention strategies for patients suffering from autoimmune disorders.