The role of schwann cell - macrophage interactions in keloid pathogenesis

Summary: Abstract Body: Emerging evidence indicates that the interaction between Schwann cells and M2 macrophages plays a pivotal role in the initiation and/or progression of keloids, a fibrotic skin disorders characterized by an excessive production of extracellular matrix (ECM). To study this process, we developed a three-dimensional in vitro model utilizing the self-secreted ECM of dermal cells derived from keloids or healthy skin. Models generated from keloid-derived cells exhibited increased production of ECM and a greater degree of collagen fiber alignment compared to those established with cells from healthy skin. Subsequently, we integrated differentially polarized macrophages into the in vitro models to evaluate their effects on Schwann cells and the reciprocal influence of Schwann cells on macrophages. Schwann cells exerted minimal, if any, influence on macrophages. In contrast, macrophages significantly affected Schwann cell gene expression in a phenotype-dependent manner, as revealed by RNA sequencing. Co-culture of Schwann cells with monocytes produced only minor effects. Co-culture with M1 macrophages induced a pro-inflammatory phenotype in Schwann cells and gene expression associated with antigen presentation. Conversely, co-culture with M2 macrophages resulted in increased expression of ECM components and factors involved in TGFβ signaling. Overall, our in vitro model replicates changes comparable to those observed in vivo in keloids, providing a valuable platform for studying the pathology and testing potential therapeutic interventions. The cross-talk of Schwann cells and M2 macrophages in keloids may represent an important mechanism, leading to increased matrix deposition, which could therefore contribute to the infinite growth of keloids. Melanie Salek¹, Tamara Weiss², Karin Pfisterer¹, Vera Vorstendlechner², Hannes Kühtreiber¹, Martin Direder³, Hendrik Ankersmit⁴, Michael Mildner¹ 1. Department of Dermatology, Medizinische Universitat Wien, Vienna, Vienna, Austria. 2. Department of Plastic and Reconstructive and Aesthetic Surgery, Medizinische Universitat Wien, Vienna, Vienna, Austria. 3. Department of Orthopedics and Trauma-Surgery, Medizinische Universitat Wien, Vienna, Vienna, Austria. 4. Department of Thoracic Surgery, Medizinische Universitat Wien, Vienna, Vienna, Austria. Stem Cell Biology, Tissue Regeneration and Wound Healing