TRR 167:  Development, function and potential of myeloid cells in the central nervous system (NeuroMac) (2017 -)

Myeloid cells in the central nervous system (CNS) represent a heterogeneous class of innate immune cells that differentially contribute to the maintenance of tissue homeostasis during development, adulthood and disease. Recent studies using cell-specific targeting, in vivo imaging, single-cel lexpression analysis and other sophisticated tools fundamentally changed our views on the origin, fate and function of distinct myeloid subsets in the CNS. In the first funding period, we have made substantial research efforts to elucidate the role of myeloid cells including microglia during brain diseases with a special focus on myeloid cell heterogeneity. Members of the CRC/TRR167 NeuroMac consortium introduced novel single-cell technologies in the field of neuroimmunology such as single-cell RNA-sequencing (scRNA-Seq), single-cellsequencing assay for transposase-accessible chromatin-sequencing (scATAC-seq), single-cell mass spectrometry (cytometry by time-of-flight [CyTOF]), which allowed us to characterize for the first time human microglia and discover targetable disease-linked microglia states. In the second funding period, we would like to draw on the resources of the first funding period. In detail, we plan to determine the molecular mechanisms that govern myeloid cell identity, and focus on the interactions of CNS myeloid cells with neurons and macroglia, which are essential to establish context-associated microglia states. The newly identified microglia clusters will now be spatially mapped in brain pathologies using cutting-edge spatial genomic and proteomic tools. We shall also use newly developed transgenic mouse models for fate mapping and gene targeting to interfere with myeloid cells functions.The long-term goal of the NeuroMac consortium is to facilitate the transfer of knowledge obtained from basic research on brain myeloid cells to the improvement of patient care by providing sufficient preclinical evidence for later ‚bench-to-bedside‘ translation and by deciphering the fundamental mechanisms of myeloid cell biology in the CNS during health and disease. In order to achieve this ambitious long-term goal, we need to provide more scientific basis by deciphering the fundamental mechanisms of myeloid cell biology in the CNS during health and disease.