Department of Dermatology, University of Rochester Medical Center, Rochester, NY, USA.
J Invest Dermatol. 2013 Apr;133(4):988-98. doi: 10.1038/jid.2012.437. Epub 2012 Dec 6.
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.
特应性皮炎（AD）的特征是表皮紧密连接（TJ）缺陷和金黄色葡萄球菌皮肤感染倾向。金黄色葡萄球菌被许多模式识别受体感知，包括 Toll 样受体 2（TLR2）。我们假设有效的先天免疫反应将包括皮肤屏障修复，而 AD 患者的这种反应受损。金黄色葡萄球菌衍生的肽聚糖（PGN）和合成 TLR2 激动剂增强了 TJ 屏障，并增加了 TJ 蛋白、闭合蛋白 1（CLDN1）、闭合蛋白 23（CLDN23）、闭合蛋白和紧密连接蛋白 1（ZO-1）在原代人角质形成细胞中的表达。TLR2 激动剂增强了经胶带剥离损伤的人表皮的皮肤屏障恢复。与非特应性受试者相比，Tlr2（-/-）小鼠在胶带剥离后屏障恢复延迟且不完全。与非特应性受试者相比，AD 受试者的表皮 TLR2 表达减少，与经皮水分丢失（TEWL）呈负相关（r=-0.654，P=0.0004）。这些观察结果表明，TLR2 激活增强了小鼠和人皮肤的皮肤屏障，是伤口修复反应的重要组成部分。在 AD 患者中观察到的表皮 TLR2 表达减少可能与其功能不全的皮肤屏障有关。
