Project manager: Dr. Andreas Wild
This group focusses on the biologic function of the CD83 molecule, expressed by specific immune cells, including DCs, Tregs as well as microglia. Using cell-type specific conditional KO (cKO) mouse strains, we demonstrated that DC-expressed CD83, plays an important part in resolution of inflammation, since autoimmune responses are severely aggravated in these cKO mice. On the other hand, due to this over activation, bacterial infections are cleared much better.
On cellular level, we found that CD83-deficent DCs are characterized by a pro-inflammatory cytokine profile and inhibited tolerogenic and regulatory processes. The underlying molecular mechanisms, leading to the differentiation of this particular cellular phenotype, are currently under investigation. In studies, using CD83 cKO Tregs, we have shown that CD83 is essential for the differentiation and stability of this particular T cell subset, and now we investigate the underlying mechanisms.
Moreover, we analyze cKO-strains, in which CD83 is specifically depleted in microglial cells, of the central nervous system (CNS). Using these mice, we have discovered that CD83 is associated with both, a homeostatic and a reparative phenotype, in these CNS cells. Currently, we are investigating the effect of CD83 deletion, using preclinical models for autoimmune neuro-inflammation and found, that CD83 cKO mice develop axacerbated disease symptoms. Within this basic research project, we will generate valuable insights to development new therapies for inflammatory autoimmune disorders of the CNS, in the future.