期刊
JOURNAL OF EXTRACELLULAR VESICLES
卷 12, 期 6, 页码 -出版社
WILEY
DOI: 10.1002/jev2.12335
关键词
atopic dermatitis; bacteria; exosomes; extracellular vesicles; filaggrin; keratinocyte; Staphylococcus aureus
类别
Filaggrin (FLG) protein plays a crucial role in maintaining the skin barrier function, but its excessive accumulation can lead to premature cell death. Researchers have discovered that small extracellular vesicles (sEVs) secreted by keratinocytes may contain filaggrin-related cargo, providing a mechanism for eliminating excess filaggrin. The bacteria Staphylococcus aureus (S. aureus) promotes the packaging and secretion of filaggrin within sEVs, facilitating its removal from the skin and potentially aiding bacterial growth.
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.
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