Neuroimmune regulation of macrophage tissue repair functions – SensoRepair

Survival of living organisms depends on their capacity to develop defence mechanisms against environmental challenges that cause tissue damage and inflammation. These protective functions involve the nervous system and the immune system, two systems traditionally considered as independent. However, a regulatory role of the nervous system on immune functions has been recently described.
The skin contains a highly developed immune system which is activated after injury, inducing an inflammatory process. Pain is one of the major signs of inflammation. Following an acute injury, inflammatory mediators activate sensory neurons present in tissues. These neurons transmit the damaging information to the brain eliciting pain. They also release a number of mediators and neuropeptides at the site of injury that can modulate immune cells present locally. Among the skin-resident immune cells, macrophages play a key role in tissue repair, but the precise molecular mechanisms that regulate their pro-inflammatory or pro-repair function remain poorly understood.
We have recently demonstrated a major role for sensory neurons in regulating the tissue repair functions of monocytes/macrophages. The goal of this project is to decipher the regulatory role of the nervous system on macrophage inflammatory and pro-repair responses in the skin. We will tackle this question by studying macrophage activities in genetically modified mice in which distinct subsets of sensory neurons will be manipulated through chemo-genetic activation, inactivation or through inducible neuronal ablation. We will also analyse the molecular basis of these neuroimmune regulations.