CD83 induced immune-regenerative effects and resolution of inflammation

Project manager: Dr. Dmytro Royzman, Prof. Dr. Alexander Steinkasserer

The timely coordinated and site specific resolution of inflammation and the subsequently induced immune-mediated regeneration processes of cells and tissues, are absolutely vital to inhibit chronification and long term damage. This is true for inflammatory disorders of the joint and intestinal tissues, such as in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), as well as for would healing processes.

Since the recombinantly expressed soluble CD83 (sCD83) molecule has been shown to induce antigen-specific immune tolerance and resolution of Inflammation, we investigated the effects of sCD83 in the context of preclinical RA models. Herein, sCD83-treated mice showed a significantly ameliorated disease progression, a reduced inflammatory milieu as well as an accelerated resolution of inflammation. Noteworthy, sCD83 treated animals were even protected from a flare up reaction, without any additional sCD83-applications.

Furthermore, we discovered for the first time, that sCD83 treated animals show an inhibitory effect on the formation of bone-resorbing cells, i.e. osteoclasts. Based on these results, the major focus of the research group lies now in the translation of these basic murine results into the human setting, in order to establish new sCD83 based therapeutic strategies for RA patients.

In addition, we investigate the pro-regenerative capacities of sCD83 in the context of wound healing. This project is based on the previous observation that both, the systemic as well as the local sCD83 application, resulted in a significantly improved and accelerated wound closure, using a murine model. In particular, this was characterized by an increased vessel formation within the wound areas and accelerated regenerative healing processes.

Currently, we investigate the sCD83-mediated molecular and cellular processes in the course of wound healing, to elucidate the underlying mechanisms. In addition, the potential of sCD83 to induce long lasting wound healing and regeneration processes, for future treatment options for elderly patients suffering from chronic wounds or patients with wound-healing disorders, will be investigated.