Neuromediators Associated With Neurogenic Skin Inflammation Promote M2 Differentiation of Macrophages in Human Skin Ex Vivo

The study investigates the effects of neuromediators like substance P (SP) and nerve growth factor (NGF) on dermal macrophages (MACs) in human scalp skin ex vivo. It was found that SP and NGFβ, along with its precursor 7S NGF, promote the differentiation of MACs into the anti-inflammatory M2 phenotype, which aids in tissue repair and limits neuroinflammation. SP enhances the number of CD68+ MACs and increases M2 MACs, potentially due to increased periostin production. NGFβ-treated skin significantly increased M2 MACs co-expressing IL-10, while both 7S NGF and NGFβ treatments decreased IL-31+ MACs, which are associated with pro-inflammatory responses. These findings suggest that SP, 7S NGF, and NGFβ could be potential targets for interventions in macrophage-dependent skin conditions.