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葡萄球菌外毒素是 IL-22 的强诱导剂:在特应性皮炎中的潜在作用。

Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis.

机构信息

Department of Dermatology and Allergy, Division of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany.

出版信息

J Allergy Clin Immunol. 2010 Dec;126(6):1176-83.e4. doi: 10.1016/j.jaci.2010.07.041.

DOI:10.1016/j.jaci.2010.07.041
PMID:20864149
Abstract

BACKGROUND

Patients with atopic dermatitis (AD) and psoriasis are frequently colonized with Staphylococcus aureus that produces staphylococcal enterotoxin B (SEB) and α-toxin. In patients with AD, S aureus colonization is positively correlated with the severity of their eczema. Moreover, IL-22-producing cells have been shown to accumulate in AD skin and to correlate with disease severity.

OBJECTIVE

To assess IL-22 production in response to SEB and sublytic α-toxin stimulation in patients with AD and psoriasis compared with healthy controls.

METHODS

IL-22 induction was investigated in PBMCs, T cells, and autologous cocultures of keratinocytes and T cells on SEB and α-toxin stimulation in a time-dependent and dose-dependent manner at the mRNA and protein (ELISA and flow cytometry) level. Anti-IL-1 receptor or anti-IL-6 antibodies were used in blocking experiments.

RESULTS

Staphylococcal enterotoxin B and sublytic α-toxin concentrations induced IL-22 production in PBMCs and isolated CD4(+) T cells. IL-22 secretion was enhanced by α-toxin stimulation in autologous cocultures of keratinocytes and T cells. In T cells and PBMCs from patients with AD, IL-22 secretion was significantly enhanced on α-toxin stimulation compared with patients with psoriasis and healthy controls.

CONCLUSION

Increased IL-22 secretion induced by staphylococcal exotoxins in the skin partially explains how skin colonization and infection with S aureus can contribute to chronic skin inflammation in AD.

摘要

背景

特应性皮炎(AD)和银屑病患者常定植有金黄色葡萄球菌,其可产生葡萄球菌肠毒素 B(SEB)和α-毒素。在 AD 患者中,金黄色葡萄球菌定植与湿疹的严重程度呈正相关。此外,已经证明 IL-22 产生细胞在 AD 皮肤中积累,并与疾病严重程度相关。

目的

评估 SEB 和亚致死α-毒素刺激对 AD 和银屑病患者与健康对照者的 IL-22 产生的影响。

方法

以时间和剂量依赖的方式,在 PBMCs、T 细胞以及角质形成细胞和 T 细胞的自体共培养物中,研究 SEB 和α-毒素刺激下 PBMCs、T 细胞对 IL-22 的诱导,在 mRNA 和蛋白(ELISA 和流式细胞术)水平上进行研究。在阻断实验中使用抗 IL-1 受体或抗 IL-6 抗体。

结果

金黄色葡萄球菌肠毒素 B 和亚致死α-毒素浓度可诱导 PBMCs 和分离的 CD4(+)T 细胞产生 IL-22。α-毒素刺激增强了自体共培养物中角质形成细胞和 T 细胞的 IL-22 分泌。与银屑病患者和健康对照组相比,AD 患者的 T 细胞和 PBMCs 中,α-毒素刺激可显著增强 IL-22 分泌。

结论

金黄色葡萄球菌外毒素在皮肤中诱导的 IL-22 分泌增加,部分解释了金黄色葡萄球菌定植和感染如何导致 AD 慢性皮肤炎症。

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