RNase L Represses Hair Follicle Regeneration Through Altered Innate Immune Signaling

The study presented at the International Conference on Orthopedics and Musculoskeletal Disorders reveals that RNase L acts as a repressor of hair follicle regeneration by altering innate immune signaling. Researchers compared human participants undergoing laser rejuvenation with Rnasel-/- mice, which showed increased regenerative capacity and enhanced wound-induced hair neogenesis (WIHN) through elevated IL-36a. The study found that inhibiting caspases pharmacologically promoted regeneration in an IL-36-dependent manner across multiple epithelial tissues. A negative feedback loop was identified where RNase L-activated caspase-1 limits the proregenerative dsRNA-TLR3 signaling by cleaving the toll-like adaptor protein TRIF. This suggests RNase L tempers immune hyperactivation during viral infections at the cost of inhibiting regeneration, highlighting its role as a regeneration repressor gene.