Zhou Hong, Tan Xi, Chen Guozhong, Liu Xinxin, Feng Aiping, Liu Zhi, Liu Wei
National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
J Invest Dermatol. 2025 Feb;145(2):312-322.e9. doi: 10.1016/j.jid.2023.02.023. Epub 2023 Mar 11.
Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder in which the skin is affected by microbial dysbiosis. The role of commensal skin microbiota in AD is of great interest. Extracellular vesicles (EVs) are important regulators of skin homeostasis and pathology. The mechanism of preventing AD pathogenesis through commensal skin microbiota-derived EVs remains poorly understood. In this study, we investigated the role of commensal skin bacterium Staphylococcus epidermidis-derived EVs (SE-EVs). We showed that SE-EVs significantly decreased the expression of proinflammatory genes (TNFα, IL1β, IL6, IL8, and iNOS) through lipoteichoic acid and increased the proliferation and migration of calcipotriene (MC903)-treated HaCaT keratinocytes. Furthermore, SE-EVs increased the expression of human β-defensins 2 and 3 in MC903-treated HaCaT cells through toll-like receptor 2, enhancing resistance to S. aureus growth. In addition, topical SE-EV application remarkably attenuated inflammatory cell infiltration (CD4 T cells and Gr1 cells), T helper 2 cytokine gene expression (Il4, Il13, and Tlsp), and IgE levels in MC903-induced AD-like dermatitis mice. Intriguingly, SE-EVs induced IL-17A CD8 T-cell accumulation in the epidermis, which may represent heterologous protection. Taken together, our findings showed that SE-EVs reduced AD-like skin inflammation in mice and may potentially be a bioactive nanocarrier for the treatment of AD.
特应性皮炎（AD）是一种慢性炎症性皮肤病，其皮肤受到微生物群落失调的影响。共生皮肤微生物群在AD中的作用备受关注。细胞外囊泡（EVs）是皮肤稳态和病理的重要调节因子。通过共生皮肤微生物群衍生的EVs预防AD发病机制仍知之甚少。在本研究中，我们调查了共生皮肤细菌表皮葡萄球菌衍生的EVs（SE-EVs）的作用。我们发现，SE-EVs通过脂磷壁酸显著降低促炎基因（TNFα、IL1β、IL6、IL8和iNOS）的表达，并增加钙泊三醇（MC903）处理的HaCaT角质形成细胞的增殖和迁移。此外，SE-EVs通过Toll样受体2增加MC903处理的HaCaT细胞中人β-防御素2和3的表达，增强对金黄色葡萄球菌生长的抵抗力。此外，局部应用SE-EV可显著减轻MC903诱导的AD样皮炎小鼠的炎性细胞浸润（CD4 T细胞和Gr1细胞）、辅助性T细胞2细胞因子基因表达（Il4、Il13和Tlsp）和IgE水平。有趣的是，SE-EVs诱导IL-17A CD8 T细胞在表皮中积聚，这可能代表异源保护。综上所述，我们的研究结果表明，SE-EVs可减轻小鼠AD样皮肤炎症，可能是一种治疗AD的生物活性纳米载体。
