Single-cell transcriptomics reveals a senescence-associated IL-6/CCR6 axis driving radiodermatitis

ABSTRACT: Irradiation-induced alopecia and dermatitis (IRIAD) are two of the most visually recognized complications of radiotherapy, of which the molecular and cellular basis remains largely unclear. By combining scRNA-seq analysis of whole-skin-derived irradiated cells with genetic ablation and molecular inhibition studies, we show that senescence-associated IL-6 and IL-1 signaling, together with IL-17 upregulation and CCR6+-mediated immune cell migration are crucial drivers of IRIAD. Bioinformatics analysis colocalized irradiation-induced IL-6 signaling with senescence pathway upregulation largely within epidermal hair follicles, basal keratinocytes, and dermal fibroblasts. Loss of cytokine signaling by genetic ablation in IL-6-/- or IL-1R-/- mice, or by molecular blockade, strongly ameliorated IR

SUBMITTER: Dr. Mor Paldor 

PROVIDER: S-SCDT-EMM-2021-15653 | biostudies-other |

REPOSITORIES: biostudies-other