Abstract
Background
Mammalian epidermis has two diffusion barriers, the stratum corneum (SC) and tight
junctions (TJs). We reported previously that a single living cell layer exists between
the SC and TJ-forming keratinocytes in mice; however, the exact location of the TJ
barrier in human epidermis has not been defined.
Objective
To investigate the precise distribution of epidermal TJs in relation to various cell–cell
junction proteins and the SC and to clarify the barrier function of TJs against macromolecules
in human skin.
Methods
The localization of various junctional proteins was investigated in human skin sections
and in the roofs of bullae formed by ex vivo exfoliative toxin (ET) treatment in three dimensions. ET and single-chain variable
fragments (scFv) against desmoglein 1 were used as large diffusion probes.
Results
Human stratum granulosum (SG) cells have a distinct distribution of TJ, adherens junction,
and desmosome proteins in the uppermost three layers (SG1–SG3 from the surface inward).
Ex vivo injection of ET or scFv demonstrated that only SG2–SG2 junctions function as a TJ
barrier, limiting the inside-out diffusion of these proteins. The roofs of bullae
formed by ex vivo ET treatment consisted of SC, SG1 cells, and TJ-forming SG2 cells, probably mimicking
bulla formation in bullous impetigo.
Conclusion
Human epidermis has three SG cell layers with distinct properties just beneath the
SC, of which only SG2 cells have functional TJs. Our results suggest that human epidermal
TJs between SG2 cells form a paracellular diffusion barrier against soluble proteins,
including immunoglobulins and bacterial toxins.
Keywords
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Article info
Publication history
Published online: May 28, 2013
Accepted:
April 17,
2013
Received in revised form:
April 10,
2013
Received:
October 31,
2012
Footnotes
☆This work was partly supported by Grants-in-Aid for Scientific Research, the “Promotion of Environmental Improvement for Independence of Young Researchers” program of the Ministry of Education, Culture, Sports, Science and Technology of Japan, Health Labour Sciences Research Grants for Research on Allergic Diseases and Immunology from the Ministry of Health, Labour and Welfare of Japan, a Keio University Grant-in-Aid for Encouragement of Young Medical Scientists, a Research Grant from the Cosmetology Research Foundation, and The Mochida Memorial Foundation for Medical and Pharmaceutical Research.
Identification
Copyright
© 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
