IL-11 Drives Dermal Fibroblast Activation in Mechanical Stretch-Mediated Skin Expansion

Skin expansion is a frequently utilized technique to produce additional skin for repairing tissue defects in many conditions, such as postburn/trauma scars. This is achieved by stimulating skin regeneration through mechanical stretch. Although the exact role of IL-11 in skin expansion remains unclear, it has been identified as a mechanical stimuli-sensitive cytokine. In this study, we demonstrated that the expressions of IL-11 and the IL-11 receptor alpha subunit were significantly increased in dermal fibroblasts of expanded skin and that low expression of IL-11 was related to poor regeneration of expanded skin. Inhibition of IL-11 signaling resulted in decreased mechanical stretch-induced fibroblast proliferation, extracellular matrix production, and myofibroblast activation in vitro as well as impaired skin regeneration during skin expansion in vivo. Mechanistically, we discovered that WNT5B functioned as a downstream regulator of IL-11-mediated cell activation in the presence of mechanical stretch. Finally, the administration of recombinant IL-11 through intradermal injection in mice significantly promoted fibroblast activation and prevented the reduction of dermal thickness during skin expansion. In summary, the results of our study demonstrated that IL-11 signaling is essential in fibroblast activation induced by mechanical stretch, making it a promising target for clinical application to enhance skin regeneration during skin expansion.