Allergy affects more than 25% of the population in industrialized countries. The pathophysiological hallmark of type I allergy is the Th2-driven production of IgE against otherwise harmless antigens (i.e. allergens) in predisposed atopic individuals. Several concepts for tolerance induction in allergy have been described. Since they are associated with substantial limitations, however, more robust tolerance strategies are needed.

In our lab, we are investigating the induction of tolerance in IgE-mediated allergy through molecular chimerism which has not been employed for this indication before.

In proof of principle studies the transplantation of syngeneic murine bone marrow retrovirally transduced to express a grass pollen allergen led to permanent molecular chimerism (i.e. persistence of hematopoietic cells expressing the allergen) and robust allergen-specific tolerance at the B cell, T cell and effector cell levels.

Building on this novel model we are interested in understanding its mechanisms of T cell and B cell tolerance and in developing advanced protocols employing transplantation of genetically modified hematopoietic cells in a clinically more relevant manner.