Injury-activated glial cells promote wound healing of the adult skin in mice

Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, many peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here we report that peripheral glia are crucially involved in this process. Using a mouse excisional wound healing model, in which we genetically fate-mapped peripheral glia, we show that injury activates peripheral glia, thereby promoting de-differentiation,cell cycle re-entry and dissemination of these cells from nerve bundles into the wound bed. Analysis of genetically traced cells demonstrated that injury-activated glia secrete a plethora of factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling. Accordingly, genetic depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion by genetic means promotes myofibroblast formation. Thus, injury-activated glia and/or their secretome might have therapeutic potential in human wound healing disorders.