title: The stratum corneum comprises three layers with distinct metal-ion barrier properties.
abstract: The stratum corneum (SC), the outermost barrier of mammalian bodies, consists of layers of cornified keratinocytes with intercellular spaces sealed with lipids. The insolubility of the SC has hampered in-depth analysis, and the SC has been considered a homogeneous barrier. Here, we applied time-of-flight secondary ion mass spectrometry to demonstrate that the SC consists of three layers with distinct properties. Arginine, a major component of filaggrin-derived natural moisturizing factors, was concentrated in the middle layer, suggesting that this layer functions in skin hydration. Topical application of metal ions revealed that the outer layer allowed their passive influx and efflux, while the middle and lower layers exhibited distinct barrier properties, depending on the metal tested. Notably, filaggrin deficiency abrogated the lower layer barrier, allowing specific metal ions to permeate viable layers. These findings elucidate the multi-layered barrier function of the SC and its defects in filaggrin-deficient atopic disease patients.
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo 160-8582, Japan. akiharu@a5.keio.jp
authors.forename: Akiharu
authors.initials: A
authors.lastname: Kubo
authors.forename: Itsuko
authors.initials: I
authors.lastname: Ishizaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Kubo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagao
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D004817:Epidermis / Q000502:physiology*; D005260:Female; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000502:physiology*; D050356:Lipid Metabolism; D013058:Mass Spectrometry / Q000379:methods; D008670:Metals / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D002412:Cations; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008670:Metals; D001120:Arginine