Interleukin 11 drives dermal fibroblast activation in mechanical stretch-mediated skin expansion

Abstract

Skin expansion is a frequently utilized technique to produce additional skin for repairing tissue defects in many conditions, such as post-burn/trauma scars. This is achieved by stimulating skin regeneration through mechanical stretch (MS). While the exact role of interleukin 11 (IL11) in skin expansion remains unclear, it has been identified as a mechanical stimuli-sensitive cytokine. In this study, we demonstrated that the expression of IL11 and IL11 receptor alpha subunit were significantly increased in dermal fibroblasts of expanded skins (ESs), and that low expression of IL11 was related to poor regeneration of ESs. Inhibition of IL11 signaling resulted in decreased MS-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 IL11-mediated cell activation in the presence of MS. Finally, the administration of recombinant IL11 via 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 IL11 signaling is essential in fibroblast activation induced by MS, making it a promising target for clinical application to enhance skin regeneration during skin expansion.

Keywords: dermal regeneration; fibroblast activation; interleukin 11; mechanical stretch; skin expansion.