Kruppel like factor KLF4 facilitates cutaneous wound healing by promoting fibrocyte generation from myeloid-derived suppressor cells

Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells (MDSCs) accumulate as a result of inflammation and promote cutaneous wound healing by mechanisms not fully understood. Recently, MDSCs have been shown to differentiate into fibrocytes which serve as emerging effector cells that enhance cell proliferation in wound healing. We postulate that in wound healing, MDSCs not only execute their immunosuppressive function to regulate inflammation, but also stimulate cell proliferation once they differentiate into fibrocytes. In the current study, using full thickness and pressure ulcer mouse models, we found that KLF4 deficiency resulted in decreased accumulation of MDSCs and fibrocytes and wound healing was significantly delayed. Conversely, KLF4 activation by the plant-derived product, Mexicanin I, increased the numbers of MDSCs and fibrocytes and accelerated wound healing. Collectively, our study revealed a previously unreported function of MDSCs in cutaneous wound healing and identified Mexicanin I as a potential agent to accelerate PU wound healing.