Control of epithelia keratinocyte proliferation is an essential component of normal wound repair. In Immunity, Gallo and colleagues report that REG3A, an antimicrobial protein known to control bacterial proliferation in the intestine, is induced in keratinocytes after acute skin injury and contributes to wound healing by inhibiting differentiation and increasing the proliferation of keratinocytes. REG3A expression is induced via signaling by IL-17 through its receptor IL-17RA and promotes wound re-epithelization by binding to its receptor EXTL3, followed by activation of the kinases PI(3)K and Akt. REG3A also has abundant expression in psoriatic lesions in the absence of acute injury in human patients and in mouse models of psoriasis. Because IL-17 also has abundant expression in psoriasis, the identification of REG3A as a stimulus for keratinocyte proliferation offers a link between IL-17-mediated inflammation and skin proliferation.

Immunity 37, 74–84 (2012)