IL-33 and ST2 in Atopic Dermatitis: Expression Profiles and Modulation by Triggering Factors
IL-33 and ST2 in Atopic Dermatitis: Expression Profiles and Modulation by Triggering Factors
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DOI：
10.1038/jid.2011.446
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发表时间：
2012-05-01
影响因子：
6.5
通讯作者：
Alenius, Harri
中科院分区：
文献类型：
--
作者：
Savinko, Terhi;Matikainen, Sampsa;Alenius, Harri
在特应性皮炎（AD）的急性期，辅助性T细胞2型（Th 2）细胞因子表征皮肤中的炎症反应。IL-33是一种新的组织来源的细胞因子，其主要由屏障组织的细胞表达，并且已知激活Th 2淋巴细胞、肥大细胞和嗜酸性粒细胞。IL-33通过由IL-33特异性受体ST 2和共受体IL-1 RAcP组成的受体复合物进行信号传导。由于已知IL-33促进Th 2型免疫，我们研究了IL-33及其受体组分在人AD皮肤、AD鼠模型和各种细胞模型中的表达谱。我们发现，在过敏原或葡萄球菌肠毒素B（SE B）暴露后，AD皮肤中IL-33和ST 2的表达增加，以及在22周龄的丝状蛋白缺陷小鼠的皮肤中。此外，皮肤成纤维细胞、HaCaT角质形成细胞、原代巨噬细胞和HUVEC内皮细胞响应于肿瘤坏死因子-α和IFN-γ的组合刺激而有效地产生IL-33，这通过双链RNA的模拟物进一步增强。最后，局部他克莫司治疗可抑制刺激物、过敏原或SEB激发引起的IL-33和ST 2表达增加。这些结果表明IL-33-ST 2相互作用在AD中的重要作用，并强调了细菌和病毒感染可能增加IL-33产生的事实。
In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-alpha and IFN-gamma, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.