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SFB 704:  Molecular Mechanisms and Chemical Modulation of Local Immune Regulation

Subject Area Biology
Chemistry
Medicine
Term from 2006 to 2017
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 15477770
 
Antigen-presenting cells are operative in the transmission of specific information to cells of the immune system. MHC restricted presentation of antigen to CD4 and CD8 T cells alone is not sufficient to convey all information necessary for the decision as to mount an immune response (immunity) or to maintain a state of immune tolerance. Functional activation of antigen-presenting cells, most notably dendritic cells, is critical as to the decision whether antigen-specific immunity is raised. However, activation is not a uniform process and different activation signals give rise to different functional phenotypes of dendritic cells, which consist of many different subpopulation. Even more, dendritic cells are subjected to functional modulation by local environmental signals. The mechanisms giving rise to the complexity of local immune regulation include recruitment of subpopulations of antigen-presenting cells with specific functional repertoires, environmental signals, which alter the functions of local antigen presenting cell populations, and signals determining positioning of antigen presenting cells in certain anatomic compartments are still mostly unknown. This initiative aims at the elucidation of local, organ-adapted functions of antigen-presenting cells and their interactions with T cells, which underlie tolerance induction and immune activation. It further aims at analysing the underlying immune signalling processes and at developing novel chemical tools to manipulate key immune regulatory molecules. The long-term goal is to selectively target organ-compartmented functions at the molecular level. Therefore, the key objectives of this proposal are:
(1) to understand local migration patterns of specific dendritic cell (DC) subpopulations and their mutual interactions with T cells,
(2) to understand the functions of organ-resident cells in the programming of immune activation versus tolerance induction,
(3) to understand and identify inter- and intracellular immune signalling functions in cell migration, activation and attenuation,
(4) to understand the role of amino-acid catabolism in switching immune functions from activation to tolerance.
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