Activation of Epidermal Toll-Like Receptor 2 Enhances Tight Junction Function: Implications for Atopic Dermatitis and Skin Barrier Repair

1] Department of Dermatology, University of Rochester Medical Center, Rochester, New York, USA [2] Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA.
Journal of Investigative Dermatology (Impact Factor: 7.22). 12/2012; 133(4). DOI: 10.1038/jid.2012.437
Source: PubMed


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.Journal of Investigative Dermatology advance online publication, 6 December 2012; doi:10.1038/jid.2012.437.

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    • "). Similar analyses of human skin samples showed pronounced TLR2 expression in human skin albeit at lower amount in AD compared to healthy skin (Figure S4A), as known from other studies (Kuo et al., 2013). Next, we analyzed the functional consequences of the TLR upregulation. "
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    • "Based on these reports, we assume that decreased TJ components in lesional AD promote epicutaneous penetration of allergens, including the house dust mite antigen, which leads to the increased possibility of developing systemic allergy or atopic march. Recently, Kuo et al.28 showed that the activation of toll-like receptor (TLR)-2, which shows reduced expressed in AD, enhances TJ function in mice and human keratinocytes, suggesting the use of TLR-2 enhancers as a potential therapeutic strategy in patients with AD. Further investigation of the crosstalk between TJs and the SC barrier is needed to clarify the role of TJs in the pathogenesis of AD. "
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