Enhancement of tolerogenic or immunostimulatory potential of dendritic cells for therapeutic goals

Abstract

Dendritic cells are the heterogeneous and versatile regulators of immune system. They possess an inherent plasticity allowing them to either prime and boost the immune responses or induce immunological tolerance. They are the most potent APCs, specialized to capture, process and present antigens to T cells. Increased knowledge about their development and function will give us more opportunities to influence the immune system to our benefit. On one hand boosting of immunity towards multitude of infectious agents as well as against cancers is of high priority while on the other hand dampening or tolerizing the specific immune responses is highly desirable in many autoimmune diseases, clinical transplantations and in gene therapy settings. The goal of this project was to engineer ‘tailor made’ DCs with either “highly tolerogenic” or “immunostimulatory” properties through genetic and cellular manipulations, which could be used as tools for cellular therapies. To do this, we exploit the recent findings that the forced expression of HOXB4 homeo domain containing protein fused to NUP98 (NUP98-HOXB4) in hematopietic stem cells and primitive progenitors increases their self-renewal capacity in culture.