Project manager: Dr. Matthias Lechmann
TSLP is thought to be the “missing link” between DC activation and allergic responses. To further analyze the role of TSLP in vivo, a TSLP KO-mouse was generated. Using this KOmouse, the function of TSLP was addressed in different inflammatory and infectious diseases models as well as in models for autoimmunity. It was demonstrated that TSLP has an important protective function in the development of chronic inflammatory bowel diseases, is capable to directly stimulate intestinal epithelial cells and promotes the regeneration of the epithelial barrier.
In the second project, the CD83-specific reporter mouse was generated which now allows us to carry out in vivo monitoring of CD83 expressing cells. In this project, the expression and function of CD83 in T cell subpopulations is of particular interest. We reported that CD83positive T cells had mainly the phenotype of regulatory T cells as well as Treg-like suppressor functions in vitro and in vivo. Based on these findings the group now investigates, using a Treg-specific conditional CD83 KO-mouse, the influence of CD83 on differentiation and function of regulatory T cells.
Third, with regard to the therapeutic application of sCD83, a study in an animal model of inflammatory bowel disease, i.e. the DNBS-induced colitis, has been performed. Interestingly sCD83 treatment ameliorated DNBS-induced colitis, whereby these animals showed less severe progress of disease and significant faster recovery. Essential for this immunomodulatory function of sCD83 was the induction of the IDO. The immunomodulatory sCD83 is also endogenously expressed in inflamed colonic tissue. The questions which cells express CD83 in the intestine and which immune cell types and intestinal epithelial cells are direct targets of CD83 as well as how CD83 modulates intestinal homeostasis and pathogenesis are currently under investigation.