Schwann cells contribute to keloid formation
Martin Direder, Tamara Weiss, Dragan Copic, Vera Vorstandlechner, Maria Laggner, Karin Pfisterer, Caterina Selina Mildner, Katharina Klas, Daniel Bormann, Werner Haslik, Christine Radtke, Matthias Farlik, Lisa E. Shaw, Bahar Golabi, Erwin Tschachler, Konrad Höetzenecker, Hendrik Jan Ankersmit, Michael Mildner
Abstract
Keloids are disfiguring, hypertrophic scars with yet poorly understood pathomechanisms, which could lead to severe functional impairments. Here we analyzed the characteristics of keloidal cells by single cell sequencing and discovered the presence of an abundant population of Schwann cells that persisted in the hypertrophic scar tissue after wound healing. In contrast to normal skin, keloidal Schwann cells show a unique, pro-fibrotic phenotype. Our data support the hypothesis that keloidal Schwann cells contribute to the formation of the extracellular matrix and are able to affect M2 polarization of macrophages. Indeed, we show that macrophages in keloids predominantly display a M2 polarization and produce factors that inhibit Schwann cell differentiation. This study suggests the contribution of a Schwann cell - macrophage cross-talk to the continuous expansion of keloids, and that targeting Schwann cells might represent an interesting novel treatment option for keloids.