PDF(Pubmed)
Abstract：
UNASSIGNED: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis).
UNASSIGNED: To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp).
UNASSIGNED: To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry.
UNASSIGNED: We identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients\' T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33.
UNASSIGNED: The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.
UNASSIGNED: To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp).
UNASSIGNED: To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry.
UNASSIGNED: We identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients\' T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33.
UNASSIGNED: The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.
摘要：
■特应性皮炎（AD）是一种慢性，具有皮肤屏障缺陷和针对无害抗原的2型免疫应答的复发性炎症性皮肤病。AD中的皮肤微生物组的特征是微生物多样性减少，葡萄球菌占主导地位，包括表皮葡萄球菌(S.表皮）。
■为了评估表皮葡萄球菌抗原是否在AD中起作用，我们筛选了候选过敏原，并研究了针对细胞外丝氨酸蛋白酶（Esp）的T细胞和体液免疫应答。
■为了确定候选过敏原，我们分析了作为IgE替代品的人血清IgG4的结合，表皮葡萄球菌胞外蛋白的二维免疫印迹和质谱。然后我们通过ELISA在健康和AD个体中测量血清IgE和IgG1与重组Esp的结合。我们还用Esp刺激来自AD患者和对照受试者的T细胞并测量分泌的细胞因子。最后,我们分析了Esp对IL-33的蛋白水解活性，并通过质谱确定了切割位点。
■我们确定Esp为表皮葡萄球菌的显性候选过敏原。Esp特异性IgE存在于人血清中；AD患者的浓度高于对照组。对Esp反应的T细胞在AD患者和健康对照中均可检测到。健康成人的T细胞应答通过IL-17、IL-22、IFN-γ、和IL-10，而AD患者的T细胞缺乏IL-17的产生，并且仅释放少量的IL-22，IFN-γ，IL-10相比之下,来自AD患者的T细胞中的Th2细胞因子释放高于健康对照。成熟的Esp裂解并激活了alarminIL-33。
■表皮葡萄球菌胞外丝氨酸蛋白酶Esp可激活IL-33。作为一种抗原,Esp在AD患者中引发2型偏倚抗体和T细胞反应。这表明表皮葡萄球菌可以通过Esp的变应原性加重AD。
■为了评估表皮葡萄球菌抗原是否在AD中起作用，我们筛选了候选过敏原，并研究了针对细胞外丝氨酸蛋白酶（Esp）的T细胞和体液免疫应答。
■为了确定候选过敏原，我们分析了作为IgE替代品的人血清IgG4的结合，表皮葡萄球菌胞外蛋白的二维免疫印迹和质谱。然后我们通过ELISA在健康和AD个体中测量血清IgE和IgG1与重组Esp的结合。我们还用Esp刺激来自AD患者和对照受试者的T细胞并测量分泌的细胞因子。最后,我们分析了Esp对IL-33的蛋白水解活性，并通过质谱确定了切割位点。
■我们确定Esp为表皮葡萄球菌的显性候选过敏原。Esp特异性IgE存在于人血清中；AD患者的浓度高于对照组。对Esp反应的T细胞在AD患者和健康对照中均可检测到。健康成人的T细胞应答通过IL-17、IL-22、IFN-γ、和IL-10，而AD患者的T细胞缺乏IL-17的产生，并且仅释放少量的IL-22，IFN-γ，IL-10相比之下,来自AD患者的T细胞中的Th2细胞因子释放高于健康对照。成熟的Esp裂解并激活了alarminIL-33。
■表皮葡萄球菌胞外丝氨酸蛋白酶Esp可激活IL-33。作为一种抗原,Esp在AD患者中引发2型偏倚抗体和T细胞反应。这表明表皮葡萄球菌可以通过Esp的变应原性加重AD。
