An innervated, vascularized and immunocompetent human skin model to study cutaneous neuroimmune interactions.

抄録

Pathogens, chemicals and autoimmunity trigger T cell-driven inflammation in the skin under control of Dendritic Cells (DCs). No in vitro human model recapitulates cutaneous immune responses, as they lack an epidermal barrier, necessary to investigate topically applied compounds, and fail to acknowledge the influence of non-immune cells on DCs and T cells. This prevents accurate pre-clinical evaluation of drugs, adjuvants or chemicals. Therefore, we created an Innervated and Vascularized immunocompetent Tissue-Engineered Skin Tissue-Engineered Skin (IV-iTES) combining all structural and functional elements of the healthy skin.

The IV-iTES integrated human keratinocytes, fibroblasts, DCs, pseudo-capillaries and sensory nerves. Structure and cell-specific markers were thoroughly characterized. Sensory nerves could be activated in situ and subsequently released neuropeptides. When exposed to sensitizers (allergens) and control molecules, cytokines were released with a pattern that reflected the properties of the chemicals. The IViTES should allow in-depth investigations on cutaneous toxicity, angiogenesis and inflammation.