Journal of Extracellular Vesicles (Jun 2023)

Excess filaggrin in keratinocytes is removed by extracellular vesicles to prevent premature death and this mechanism can be hijacked by Staphylococcus aureus in a TLR2‐dependent fashion

  • Adrian Kobiela,
  • Lilit Hovhannisyan,
  • Paulina Jurkowska,
  • Jorge Bernardino dela Serna,
  • Aleksandra Bogucka,
  • Milena Deptuła,
  • Argho Aninda Paul,
  • Kinga Panek,
  • Ewa Czechowska,
  • Michał Rychłowski,
  • Aleksandra Królicka,
  • Jacek Zieliński,
  • Susanne Gabrielsson,
  • Michał Pikuła,
  • Magdalena Trzeciak,
  • Graham S Ogg,
  • Danuta Gutowska‐Owsiak

DOI
https://doi.org/10.1002/jev2.12335
Journal volume & issue
Vol. 12, no. 6
pp. n/a – n/a

Abstract

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Abstract 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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