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| Home > Institute Collections > W500 > Single-cell transcriptomics reveals a senescence-associated IL-6/CCR6 axis driving radiodermatitis. |
| Home > Institute Collections > W500 > Single-cell transcriptomics reveals a senescence-associated IL-6/CCR6 axis driving radiodermatitis. |
| Journal Article | DKFZ-2025-02502 |
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2022
Nature Publishing Group UK
[London]
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 IRIAD, as did deficiency of CCL20/CCR6-mediated immune cell migration in CCR6-/- mice. Moreover, IL-6 deficiency strongly reduced IL-17, IL-22, CCL20, and CCR6 upregulation, whereas CCR6 deficiency reciprocally diminished IL-6, IL-17, CCL3, and MHC upregulation, suggesting that proximity-dependent cellular cross talk promotes IRIAD. Therapeutically, topical application of Janus kinase blockers or inhibition of T-cell activation by cyclosporine effectively reduced IRIAD, suggesting the potential of targeted approaches for the treatment of dermal side effects in radiotherapy patients.
Keyword(s): Animals (MeSH) ; Interleukin-17: genetics (MeSH) ; Interleukin-17: metabolism (MeSH) ; Interleukin-6: genetics (MeSH) ; Mice (MeSH) ; Radiodermatitis (MeSH) ; Receptors, CCR6: genetics (MeSH) ; Receptors, CCR6: metabolism (MeSH) ; Transcriptome (MeSH) ; CCR6 ; IL-6 ; alopecia ; radiodermatitis ; senescence ; CCR6 protein, mouse ; Interleukin-17 ; Interleukin-6 ; Receptors, CCR6
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