Yerkovich Stephanie T, Roponen Marjut, Smith Miranda E, McKenna Kathy, Bosco Anthony, Subrata Lily S, Mamessier Emilie, Wikström Matthew E, Le Souef Peter, Sly Peter D, Holt Patrick G, Upham John W
Telethon Institute for Child Health Research, Centre for Child Health Research, Faculty of Medicine and Dentistry, University of Western Australia, Perth, Australia.
J Allergy Clin Immunol. 2009 Jan;123(1):209-216.e4. doi: 10.1016/j.jaci.2008.09.009. Epub 2008 Oct 22.
Dendritic cells (DCs) are important in allergic diseases such as asthma, although little is known regarding the mechanisms by which DCs induce T(H)2-polarized responses in atopic individuals. It has been suggested that intrinsic properties of allergens can directly stimulate T(H)2 polarizing functions of DCs, but little is known of the underlying mechanisms.
To identify novel genes expressed by house dust mite (HDM) allergen-exposed DCs.
We screened for allergen-induced gene expression by microarray, and validated differentially expressed genes at the mRNA and protein levels.
Thrombomodulin (CD141, blood dendritic cell antigen 3) expression by microarray was higher on HDM-stimulated DCs from atopic (relative to nonatopic) individuals. These findings were confirmed at both the mRNA and protein levels in an independent group. Purified thrombomodulin(+) DCs induced a strongly T(H)2-polarized cytokine response by allergen-specific T cells compared with DCs lacking thrombomodulin. In vivo, thrombomodulin(+) circulating DCs were significantly more frequent in subjects with HDM allergy and asthma, compared with control subjects. Furthermore, thrombomodulin expression in blood leukocytes was higher in children with acute asthma than at convalescence 6 weeks later.
Thrombomodulin expression on DCs may be involved in the pathogenesis of atopy and asthma.
树突状细胞（DCs）在诸如哮喘等过敏性疾病中起重要作用，尽管对于DCs在特应性个体中诱导T(H)2极化反应的机制知之甚少。有人提出变应原的内在特性可直接刺激DCs的T(H)2极化功能，但对其潜在机制了解甚少。
鉴定暴露于屋尘螨（HDM）变应原的DCs所表达的新基因。
我们通过微阵列筛选变应原诱导的基因表达，并在mRNA和蛋白质水平验证差异表达的基因。
通过微阵列检测发现，来自特应性（相对于非特应性）个体的HDM刺激的DCs上血栓调节蛋白（CD141，血液树突状细胞抗原3）的表达更高。这些发现在一个独立组的mRNA和蛋白质水平均得到证实。与缺乏血栓调节蛋白的DCs相比，纯化的血栓调节蛋白阳性DCs诱导变应原特异性T细胞产生强烈的T(H)2极化细胞因子反应。在体内，与对照受试者相比，HDM过敏和哮喘患者中血栓调节蛋白阳性循环DCs明显更常见。此外，急性哮喘患儿血液白细胞中的血栓调节蛋白表达高于6周后恢复期。
DCs上血栓调节蛋白的表达可能参与特应性和哮喘的发病机制。
