Schwann cells contribute to keloid formation

Due to limited availability of proper models to study keloid development, the underlying pathomechanisms of this severe skin disease is still poorly understood. Here we performed single-cell sequencing of keloids and identified the occurrence of a so far unrecognized keloidal Schwann cell population, remaining in the scar tissue after wound healing. In contrast to normal skin, keloidal Schwann cells possess a repair-like phenotype and high cellular plasticity. Our data reveal that keloidal Schwann cells directly contribute to the formation of the extracellular matrix and affect M2 polarization of macrophages. Indeed, we show that macrophages in keloids predominantly display a M2 polarization and produce factors inhibiting Schwann cell differentiation. Our data suggest that this cross-talk contribute to the infinite growth of keloids and that targeting Schwann cells might represent a novel treatment option for keloids. Single cell RNA-sequencing gene expression comparison of keloid tissue with normal scars and healthy skin. Single-cell suspension from four keloids, one normal skin and three normal scars were prepared using MACS Miltenyi Whole Skin Dissociation Kit (Miltenyi). Libraries were generated using Chromium Next GEM Single Cell 3´GEM, Library & Gel Bead Kit v3.1, Chromium Nexxt GEM Chip G Single Cell Kit and Single Index Kit T Set A (all 19x Genomics, Pleasanton, CA, USA). Data were analysed in combination with healthy skin data from Tabib et al. 2018 (PMID:29080679) as well as neurofibroma data from Brosseau et al. 2021 (PMID: 33413690)