TY - JOUR
T1 - Activation of epidermal toll-like receptor 2 enhances tight junction function
T2 - Implications for atopic dermatitis and skin barrier repair
AU - Kuo, I. Hsin
AU - Carpenter-Mendini, Amanda
AU - Yoshida, Takeshi
AU - McGirt, Laura Y.
AU - Ivanov, Andrei I.
AU - Barnes, Kathleen C.
AU - Gallo, Richard L.
AU - Borkowski, Andrew W.
AU - Yamasaki, Kenshi
AU - Leung, Donald Y.
AU - Georas, Steve N.
AU - De Benedetto, Anna
AU - Beck, Lisa A.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2012.437
DO - 10.1038/jid.2012.437
M3 - Article
C2 - 23223142
AN - SCOPUS:84875220580
SN - 0022-202X
VL - 133
SP - 988
EP - 998
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -