Neutrophils as the cornerstone between sensory neurons and regenerative fibroblasts in skin wound healing – NEUTROPHEAL

Cutaneous lesions are associated with the inability to reform a protective dermis and the formation of a fibrotic scar. Using an original mouse model of skin injury where regeneration
takes place in the center of the lesion while the periphery remains fibrotic, we have demonstrated that mesenchymal stromal c cells (i.e. fibroblasts) activate a specific transcriptomic
program and different functions depending on their location in the injury site. More recently, we have shown that neutrophils, more particularly immature neutrophils, upstream of the activation of fibroblasts, also improve the regeneration of the dermis and hair follicles. Our data as well as recent work in the literature show that the sensory nerves innervating the skin (i.e. nociceptors) are involved in maintaining skin homeostasis upon injury, by controlling the resident and recruited immune cells, including neutrophils and that they may also be involved in tissue regeneration processes. In our NEUTROPHEAL project, we propose to study the interactions between neutrophils, nociceptors and fibroblasts during the skin wound healing process. By combining our expertise in dermatology, neuroimmunology and mesenchymal stromal cells, we aim to understand how the neutrophils/nociceptors/fibroblasts triad communicate with each other in order to improve tissue regeneration at the expense of fibrosis. Ultimately, we hope that this integrative study will reveal treatments that could benefit millions of patients suffering from serious skin lesions such as burns and skin trauma.