Attraction and role of innate immune cells in brain injury. – ATTRACT

Brain injury is inflicted after stroke and many patients suffer from ill-repaired brain lesions after this event. Chemokine CXCL12 has been implicated in reorganization of damaged tissues including brain. It is expressed in cerebral vascular endothelial cells and is dramatically upregulated within the region of a brain injury. Although many immune cells expressing the CXCL12 receptor CXCR4 are attracted towards brain lesions, a causal relationship between cerebral CXCL12 and immune cell recruitment has not been established. Here, we focus on innate immune cells expressing CXCR4, namely innate lymphoid cells (ILCs) and bone marrow-derived macrophages (BMdM). ILCs have been discovered only recently, and very little is known about their role in brain injury. Also the function of BMdM specifically in the lesioned brain is still unclear since it is almost impossible to distinguish them from reactive microglia. We generated a novel cell fate mapping strategy which enables us to identify specifically invading BMdM without labelling resident microglia. In addition, we established several genetic mouse models to interfere with the CXCL12/CXCR4 pathway in cell populations of interest. With these unique tools, we will be able to study spatial and temporal patterns of innate immune cell recruitment, interaction of innate immune cells and the role of CXCL12 in damage and functional recovery in established models of focal cerebral ischemia. This project will provide new insights into the fundamental immune processes during stroke in order to focus treatments in the future.