RNase L Represses Hair Follicle Regeneration Through Altered Innate Immune Signaling

    February 2025 in “ Journal of Clinical Investigation ”
    Charles S. Kirby, Nasif Islam, Eric M. Wier, Martin P. Alphonse, Evan Sweren, Gaofeng Wang, Haiyun Liu, Dongeon Kim, Ang Li, Sam Lee, Andrew M. Overmiller, Yingchao Xue, Sashank Reddy, Nathan K. Archer, Lloyd Miller, Jianshi Yu, Weiliang Huang, Jace W. Jones, Sooah Kim, Maureen A. Kane, Robert H. Silverman, Luis A. Garza
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    Studysummary This study found that RNase L acts as a regeneration repressor gene in mammals, as seen in Rnasel-/- mice which showed increased regenerative capacity and elevated Wound Induced Hair Neogenesis through enhanced IL-36α signaling, suggesting a tradeoff between regeneration and immune regulation. Our plain-language summary of this paper — not a Tressless recommendation.
    The study explores the role of RNase L in hair follicle regeneration, identifying it as a repressor gene that affects regeneration by altering immune signaling. In both human subjects and Rnasel-/- mice, the absence of RNase L was found to enhance regenerative capacity through increased Wound Induced Hair Neogenesis (WIHN) and elevated IL-36α levels. The research describes a negative feedback loop where RNase L activates caspase-1, which limits pro-regenerative dsRNA-TLR3 signaling by cleaving the toll-like adaptor protein TRIF. Inhibiting caspases pharmacologically was shown to promote regeneration in an IL-36 dependent manner across various epithelial tissues. The study suggests that RNase L balances immune activation during viral infections but at the cost of inhibiting regeneration, indicating potential therapeutic strategies for hair growth and hair loss conditions.
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