Experimental and Translational Immunology Group, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, University of Gdansk, Gdansk, Poland.
National Heart and Lung Institute, Imperial College London, London, UK.
J Extracell Vesicles. 2023 Jun;12(6):e12335. doi: 10.1002/jev2.12335.
Filaggrin (FLG) protein is indispensable for multiple aspects of the epidermal barrier function but its accumulation in a monomeric filaggrin form may initiate premature keratinocytes death; it is unclear how filaggrin levels are controlled before the formation of storing keratohyalin granules. Here we show that keratinocyte-secreted small extracellular vesicles (sEVs) may contain filaggrin-related cargo providing a route of eliminating excess filaggrin from keratinocytes; blocking of sEV release has cytotoxic effects on those cells. Filaggrin-containing sEVs are found in plasma in both healthy individuals and atopic dermatitis patients. Staphylococcus aureus (S. aureus) enhances packaging and secretion of filaggrin-relevant products within the sEVs for enhanced export via a TLR2-mediated mechanism which is also linked to the ubiquitination process. This filaggrin removal system, preventing premature keratinocyte death and epidermal barrier dysfunction, is exploited by S. aureus which promotes filaggrin elimination from the skin that could help safeguard bacterial growth.
丝聚合蛋白（FLG）蛋白对于表皮屏障功能的多个方面都是必不可少的，但它以单体丝聚合蛋白的形式积累可能会引发角质形成细胞过早死亡；在形成储存角蛋白颗粒之前，丝聚合蛋白水平如何被控制尚不清楚。在这里，我们表明，角质形成细胞分泌的小细胞外囊泡（sEVs）可能含有与丝聚合蛋白相关的货物，为从角质形成细胞中消除多余的丝聚合蛋白提供了一种途径；阻断 sEV 的释放对这些细胞具有细胞毒性作用。含有丝聚合蛋白的 sEVs 存在于健康个体和特应性皮炎患者的血浆中。金黄色葡萄球菌（S. aureus）通过 TLR2 介导的机制增强 sEV 内与丝聚合蛋白相关产品的包装和分泌，从而增强其通过该途径的输出，该机制也与泛素化过程有关。这种丝聚合蛋白清除系统可防止角质形成细胞过早死亡和表皮屏障功能障碍，被金黄色葡萄球菌利用，促进丝聚合蛋白从皮肤中的清除，这有助于保护细菌的生长。
