Langerin+ Dendritic Cells in Cutaneous Fibrosis: The TGF-β1 Signaling Axis

Xiong Lv, Chun Xiang, Yan Zheng, Xu-Ling Lv, Wan-Xuan Zhou Department of Plastic Surgery, Quzhou People’s Hospital (Quzhou Affiliated Hospital of Wenzhou Medical University), Quzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Wan-Xuan Zhou, Email [email protected]: Cutaneous fibrosis – including hypertrophic scars and keloids – arises when immune, epithelial, and stromal signals fail to re-equilibrate after injury. Langerin+ dendritic cells (DCs) – epidermal Langerhans cells and dermal cDC1 – sit at the center of this process. These DC subsets generate latent transforming growth factor-β 1 (TGF-β 1) that keratinocyte integrins αvβ 6/αvβ 8 locally activate, creating an epidermal “cytokine gate” that restrains immunity in homeostasis yet seeds fibrosis when overdriven. Downstream, active TGF-β 1 cooperates with mechanosensitive YAP/TAZ to drive fibroblast activation and matrix stiffening, while immune skewing (Th2/Th17/Treg and M2 macrophages) sustains a pro-fibrotic milieu. We synthesize how epithelial integrins, DC programs, and fibroblast mechanotransduction converge on TGF-β 1; compare normal wound resolution with hypertrophic scar and keloid; highlight insights from single-cell and spatial omics; and outline therapeutic strategies targeting the αv integrin–TGF-β 1 axis, YAP/TAZ, and immune cues. Framing cutaneous fibrosis through a DC-centric lens clarifies testable hypotheses and points toward mechanism-guided, combinatorial therapies.Keywords: cutaneous fibrosis, Langerin+ dendritic cells, TGF-β 1 activation, hypertrophic scar, keloid, extracellular matrix remodeling