Molecular and functional characterization of nerve-modulated macrophages in the intestine

Macrophages are present in all tissues and act as essential gatekeepers of tissue homeostasis in addition to their role in host defense. Depending on the tissue in which they reside, macrophages carry out diverse and context-dependent tasks that meet the functional requirements of a specific tissue. In particular, macrophages in the central nervous system, termed microglia, carry out highly specialized tasks to support surrounding nervous tissue. In recent experiments, we identified a yet unidentified macrophage subset in the gastrointestinal tract that strongly resembles microglia in the brain. Its strategic location within the enteric nervous system together with its morphological and molecular similarities to microglia indeed suggest that these macrophages have similar functions. The general aim of this project is to acquire in-depth knowledge on the molecular and functional profile of this newly identified macrophage subset, which we call nerve-modulated macrophages. The outcome of this project will not only add tremendously to the emerging field of macrophage biology, but will also lead to the identification of the mechanisms involved in the immune-modulatory effect of vagus nerve stimulation (and enteric neurons) and will ultimately lead to novel targets and treatments for immune-mediated diseases.