Activation of epidermal toll-like receptor 2 enhances tight junction function: Implications for atopic dermatitis and skin barrier repair

I. Hsin Kuo, Amanda Carpenter-Mendini, Takeshi Yoshida, Laura Y. McGirt, Andrei I. Ivanov, Kathleen C. Barnes, Richard L. Gallo, Andrew W. Borkowski, Kenshi Yamasaki, Donald Y. Leung, Steve N. Georas, Anna De Benedetto, Lisa A. Beck

Research output: Contribution to journalArticle

Abstract

Atopic dermatitis (AD) is characterized by epidermal tight junction (TJ) defects and a propensity for Staphylococcus aureus skin infections. S. aureus is sensed by many pattern recognition receptors, including Toll-like receptor 2 (TLR2). We hypothesized that an effective innate immune response will include skin barrier repair, and that this response is impaired in AD subjects. S. aureus-derived peptidoglycan (PGN) and synthetic TLR2 agonists enhanced TJ barrier and increased expression of TJ proteins, claudin-1 (CLDN1), claudin-23 (CLDN23), occludin, and Zonulae occludens 1 (ZO-1) in primary human keratinocytes. A TLR2 agonist enhanced skin barrier recovery in human epidermis wounded by tape stripping. Tlr2 -/- mice had a delayed and incomplete barrier recovery following tape stripping. AD subjects had reduced epidermal TLR2 expression as compared with nonatopic subjects, which inversely correlated (r=-0.654, P=0.0004) with transepidermal water loss (TEWL). These observations indicate that TLR2 activation enhances skin barrier in murine and human skin and is an important part of a wound repair response. Reduced epidermal TLR2 expression observed in AD patients may have a role in their incompetent skin barrier.

Original languageEnglish (US)
Pages (from-to)988-998
Number of pages11
JournalJournal of Investigative Dermatology
Volume133
Issue number4
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Kuo, I. H., Carpenter-Mendini, A., Yoshida, T., McGirt, L. Y., Ivanov, A. I., Barnes, K. C., Gallo, R. L., Borkowski, A. W., Yamasaki, K., Leung, D. Y., Georas, S. N., De Benedetto, A., & Beck, L. A. (2013). Activation of epidermal toll-like receptor 2 enhances tight junction function: Implications for atopic dermatitis and skin barrier repair. Journal of Investigative Dermatology, 133(4), 988-998. https://doi.org/10.1038/jid.2012.437