Bi Omera, Caballero-Lima David, Sikkink Stephen, Westgate Gill, Kauser Sobia, Elies Jacobo, Thornton M Julie
Centre for Skin Sciences, Faculty of Life Science, University of Bradford, Bradford, UK.
Labskin UK, York Biotech Campus, Sand Hutton, UK.
Exp Dermatol. 2025 Mar;34(3):e70071. doi: 10.1111/exd.70071.
In addition to producing melanin to protect epidermal keratinocytes against DNA damage, melanocytes may have important roles in strengthening innate immunity against pathogens. We have developed a functional, pigmented, human full-thickness 3D skin equivalent to determine whether the presence of melanocytes impacts epidermal bacterial growth and regulates the expression of genes involved in the immune response. We introduced primary epidermal melanocytes to construct a 3-cell full-thickness skin equivalent with primary dermal fibroblasts and epidermal keratinocytes. Immunohistochemistry verified the appropriate ratio and spatial organisation of melanocytes. Alpha-MSH induced melanogenesis, confirming an appropriate physiological response. We compared this 3-cell skin equivalent with the 2-cell version without melanocytes in response to inoculation with 3 species of bacteria: Staphylococcus epidermidis, Corynebacterium striatum, and Cutibacterium acnes. There was a significant decrease in the colonisation of bacteria in the skin equivalents containing functional melanocytes. There was increased expression of immune-response genes (S100A9, DEFB4A, IL-4R) following microorganism exposure; however, there were marked differences between the unpigmented and pigmented skin equivalents. This physiologically relevant human 3D-skin equivalent opens up new avenues for studying complex skin pigmentation disorders, melanoma, and UV damage, as well as the rapidly evolving field of the skin microbiome and the balance between commensal and pathogenic species.
除了产生黑色素以保护表皮角质形成细胞免受DNA损伤外，黑素细胞在增强针对病原体的先天免疫方面可能也发挥着重要作用。我们开发了一种具有功能且有色素沉着的人全层3D皮肤等效物，以确定黑素细胞的存在是否会影响表皮细菌生长，并调节参与免疫反应的基因表达。我们引入原代表皮黑素细胞，与原代真皮成纤维细胞和表皮角质形成细胞构建三细胞全层皮肤等效物。免疫组织化学验证了黑素细胞的适当比例和空间组织。α-促黑素诱导了黑素生成，证实了适当的生理反应。我们将这种三细胞皮肤等效物与不含黑素细胞的双细胞版本进行比较，以观察其对三种细菌接种的反应：表皮葡萄球菌、纹带棒状杆菌和痤疮丙酸杆菌。含有功能性黑素细胞的皮肤等效物中细菌定植显著减少。微生物暴露后免疫反应基因（S100A9、DEFB4A、IL-4R）的表达增加；然而，无色素和有色素的皮肤等效物之间存在明显差异。这种具有生理相关性的人3D皮肤等效物为研究复杂的皮肤色素沉着障碍、黑色素瘤和紫外线损伤，以及迅速发展的皮肤微生物组领域和共生菌与致病菌之间的平衡开辟了新途径。
