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

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-β1 (TGF-β1) that keratinocyte integrins αvβ6/αvβ8 locally activate, creating an epidermal "cytokine gate" that restrains immunity in homeostasis yet seeds fibrosis when overdriven. Downstream, active TGF-β1 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-β1; 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-β1 axis, YAP/TAZ, and immune cues. Framing cutaneous fibrosis through a DC-centric lens clarifies testable hypotheses and points toward mechanism-guided, combinatorial therapies.