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CRC 1054 - Control and plasticity of cell-fate decisions in the immune system

  • Speaker: Professor Dr. Thomas Brocker
  • Affiliation: Institute for Immunology
  • Support: since 2013

T lymphocytes play a central role in immune defence, but are also involved in immune-mediated diseases. Tumor diseases or chronic infections are often associated with inefficient T-cell responses, while excessive T-cell activity can trigger autoimmune diseases and allergies. Although all these diseases affect a significant percentage of the world's population, the reasons for this failure of immunological control are largely unknown. In order to proliferate dormant antigen-specific T cells by cell division and convert them into effector cells, they must be activated by professional antigen-presenting cells such as dendritic cells. During this process, naive progenitor cells differentiate into efficient effector and memory T cells with specific capabilities. The quality of the adaptive immune response is decisively controlled by the recognition of microbial products by dendritic cells. Subsequently, dendritic cells differentiate into specialized subpopulations, which in turn control immune responses tailored to eliminate various microbial pathogens or virally infected cells. The differentiation of functionally different T cells and dendritic cells is thus a central element of any adaptive immune response. In recent years, several new and functionally different subpopulations have been discovered within the family of dendritic cells. At the same time, a growing number of studies suggests that there are also many more specialized T cell subpopulations than originally thought. The common denominator is that both dendritic cells and T cells maintain a high degree of plasticity. The biological benefit of this plasticity probably lies in the ability to adapt functional programmes to new infection events or stimuli. The present SFB initiative has set itself the task of investigating the control and plasticity of differentiation decisions in the immune system. The aim is to identify signals that determine the stability and flexibility of cell differentiation processes. Furthermore, the molecular basis of the decoding of these signals will be characterized. To this end, we bring together research groups with proven expertise in molecular and cellular immunology with stem cell researchers and vaccine developers and their respective core technologies. The research goal of this SFB is the identification of central switching elements of the immune system. In the medium to long term, this should provide the opportunity to use manipulation of immune cell differentiation for therapy. Against this background, expertise in screening and optimization of small molecule drugs as well as crystallography was integrated into the SFB proposal. The findings of this SFB should, for example, show possibilities to exploit the plasticity of immune cell differentiation processes in order, for example, to reactivate "exhausted" T cells in chronic infections or to selectively manipulate cell differentiation decisions for the treatment of chronic inflammatory diseases, allergies, autoimmunity or cancer.

Quelle: DFG Gepris