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 molecula

SUBMITTER: Paldor M 

PROVIDER: S-EPMC9358397 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature