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

Area of Science:

• Regenerative Medicine
• Dermatology
• Cell Biology

Background:

• Skin expansion is vital for tissue repair, relying on mechanical stretch to stimulate regeneration.
• The role of Interleukin-11 (IL-11), a mechanical stimuli-sensitive cytokine, in skin expansion was previously unclear.

Purpose of the Study:

• To investigate the role of IL-11 signaling in mechanical stretch-induced skin regeneration.
• To elucidate the downstream mechanisms of IL-11 in fibroblast activation.

Main Methods:

• Quantified IL-11 and its receptor expression in expanded skin dermal fibroblasts.
• Inhibited IL-11 signaling in vitro and in vivo to assess its impact on fibroblast behavior and skin regeneration.
• Investigated downstream signaling pathways, including WNT5B.
• Administered recombinant IL-11 in a mouse model.

Main Results:

• IL-11 and its receptor alpha subunit expression increased in expanded skin fibroblasts.
• Low IL-11 expression correlated with poor skin regeneration.
• IL-11 inhibition impaired fibroblast proliferation, extracellular matrix production, and myofibroblast activation.
• WNT5B was identified as a downstream mediator of IL-11 signaling.
• Recombinant IL-11 administration enhanced fibroblast activation and maintained dermal thickness in mice.

Conclusions:

• IL-11 signaling is essential for fibroblast activation in response to mechanical stretch.
• IL-11 is a critical factor promoting skin regeneration during expansion.
• Targeting IL-11 signaling presents a promising therapeutic strategy for enhancing skin repair.