Emmy Noether Junior Research Group - Organ-specific tasks of mononuclear phagocytes in health and pathology

• Project Leader: Dr. Barbara Schraml
• Affiliation: Walter-Brendel-Centre of Experimental Medicine
• Funding: since 2014

Mononuclear phagocytes are cells of the innate immune system with important functions in immune regulation and tissue homeostasis and are therefore an attractive starting point for the development of immune therapies. These include dendritic cells, monocytes and macrophages. Current research indicates that mononuclear phagocytes are functionally and ontogenetically heterogeneous. At present, there are no methods or model systems that allow their exact differentiation in vivo and therefore it is unclear whether subpopulations perform specific functions in the immune system. However, further information on the heterogeneity of mononuclear phagocytes is needed to understand their exact organ-specific functions in the immune system. Mononuclear phagocytes, for example, form a complex network in the kidney that runs through the entire organ. During kidney disease or trauma, mononuclear phagocytes contribute to inflammation and damage the organ. This can lead to the loss of renal function (renal insufficiency) and is a frequent and cost-intensive problem in hospitals, as there are hardly any therapies that promote the healing process. The aim of this proposal is to better characterise the functions of mononuclear phagocytes in humans and mice and to investigate the extent to which certain functions are determined by ontogenesis or are primarily influenced by the organ-specific environment. This problem is dealt with using the example of the kidney, whereby similar questions also apply to other tissues. The successful generation of a mouse model with which dendritic cells can be identified on the basis of their ancestry of ontogenic precursors forms the basis for the studies applied for. This model enables dendritic cells to be differentiated from other mononuclear phagocytes independently of phenotype or function for the first time. Subpopulations of mononuclear phagocytes in the healthy and diseased kidney of the mouse will be identified using this model and their function will be investigated. In addition, the generation of new mouse models, which allow phenotypically identical subpopulations of different ancestry to be specifically removed, will help to define the functions of mononuclear phagocytes in the immune system. Such identified subpopulations and their functions shall be correlated with those in the human kidney. Innovative research methods and the latest technologies will be used. These studies will significantly expand our knowledge about the role of mononuclear phagocytes in the immune system and thus create the prerequisites for new immunotherapeutic applications.

Source: GEPRIS (Text), University Hospital(Picture)