Single-Cell Transcriptomics Reveals a Senescence-Associated IL-6/CCR6 Axis Driving Radiodermatitis

    July 2022 in “ EMBO molecular medicine ”
    Mor Paldor, Orr Levkovitch-Siany, Dana Eidelshtein, Revital Adar, Claes D. Enk, Yitzhak Marmary, Sharona Elgavish, Yuval Nevo, Hadar Benyamini, Inbar Plaschkes, Shoshana Klein, Alex Mali, Stefan Rose-John, Amnon Peled, Eithan Galun, Jonathan H. Axelrod
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    TLDR Blocking certain immune signals can reduce skin damage from radiation therapy.
    The study investigates the molecular mechanisms behind irradiation-induced alopecia and dermatitis (IRIAD) using single-cell RNA sequencing (scRNA-seq) and genetic/molecular inhibition studies. It identifies senescence-associated IL-6 and IL-1 signaling, along with IL-17 upregulation and CCR6+ immune cell migration, as key drivers of IRIAD. Genetic ablation of IL-6, IL-1R, or CCR6, as well as molecular blockade, significantly reduced IRIAD in mice. The study also shows that IL-6 deficiency decreases IL-17, IL-22, CCL20, and CCR6 levels, while CCR6 deficiency reciprocally reduces IL-6, IL-17, CCL3, and MHC upregulation. Therapeutically, Janus kinase blockers and cyclosporine A effectively ameliorated IRIAD, suggesting potential targeted treatments for radiotherapy-induced skin side effects.
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