ABSTRACT

Probiotics offer various health benefits. Lactobacillus plantarum has been used for decades to enhance human intestinal mucosal immunity and improve skin barrier integrity. Extracellular vesicles (EVs) derived from eukaryotic or prokaryotic cells have been recognized as efficient carriers for delivery of biomolecules to recipient cells, and to efficiently regulate human pathophysiology. However, the mechanism underlying the beneficial effects of probiotic bacteria-derived EVs on human skin is unclear. Herein, we investigated how L. plantarum-derived EVs (LEVs) exert beneficial effects on human skin by examining the effect of LEVs on cutaneous immunity, particularly on macrophage polarization. LEVs promoted differentiation of human monocytic THP1 cells towards an anti-inflammatory M2 phenotype, especially M2b, by inducing biased expression of cell-surface markers and cytokines associated with M2 macrophages. Pre- or post-treatment with LEVs under inflammatory M1 macrophage-favouring conditions, induced by LPS and interferon-γ, inhibited M1-associated surface marker, HLA-DRα expression. Moreover, LEV treatment significantly induced expression of macrophage-characteristic cytokines, IL-1β, GM-CSF and the representative anti-inflammatory cytokine, IL-10, in human skin organ cultures. Hence, LEVs can trigger M2 macrophage polarization in vitro, and induce an anti-inflammatory phenomenon in the human skin, and may be a potent anti-inflammatory strategy to alleviate hyperinflammatory skin conditions.

摘要

益生菌具有多种健康益处。植物乳杆菌已被用于增强人类肠道粘膜免疫力和改善皮肤屏障完整性的数十年历史。源自真核或原核细胞的细胞外囊泡（EVs）已被视为有效的载体，可将生物分子传递至受体细胞，并有效地调节人体病理生理。然而，益生菌衍生的电动汽车对人体皮肤有益作用的潜在机制尚不清楚。在这里，我们调查了植物乳杆菌衍生的电动汽车（LEV）通过检查LEV对皮肤免疫力，特别是对巨噬细胞极化的影响，对人体皮肤产生有益的作用。LEV通过诱导与M2巨噬细胞相关的细胞表面标志物和细胞因子的偏向表达，促进人类单核细胞THP1细胞向抗炎M2表型，特别是M2b的分化。在LPS和干扰素-γ诱导下，在炎症性M1巨噬细胞嗜好条件下用LEV预处理或后抑制M1相关表面标志物HLA-DRα的表达。而且，LEV治疗显着诱导人皮肤器官培养物中巨噬细胞特征性细胞因子IL-1β，GM-CSF和代表性抗炎细胞因子IL-10的表达。因此，LEV可以触发M2巨噬细胞极化在体外，并在人体皮肤中引起抗炎现象，并且可能是缓解高炎症性皮肤状况的有效抗炎策略。