Single-Cell Transcriptomics Reveals a Senescence-Associated IL-6/CCR6 Axis Driving Radiodermatitis
July 2022
in “
EMBO molecular medicine
”
irradiation-induced alopecia dermatitis single-cell RNA sequencing scRNA-seq senescence-associated IL-6 IL-1 signaling IL-17 upregulation CCR6+ immune cell migration genetic ablation IL-1R molecular blockade IL-17 IL-22 CCL20 CCR6 CCL3 MHC upregulation Janus kinase blockers cyclosporine A IRIAD IL-6 IL-1 Janus kinase inhibitors cyclosporine
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.
