Shilling Rebecca A, Pinto Jayant M, Decker Donna C, Schneider Daniel H, Bandukwala Hozefa S, Schneider Jeffrey R, Camoretti-Mercado Blanca, Ober Carole, Sperling Anne I
Section of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Chicago, IL 60637, USA.
J Immunol. 2005 Aug 15;175(4):2061-5. doi: 10.4049/jimmunol.175.4.2061.
The establishment of ICOS as an important regulator of Th2 development and effector function makes the ICOS locus an attractive candidate for Th2-mediated diseases, such as asthma and allergy. In evaluation of this candidate locus in humans, we identified 11 variants and determined that two in the putative promoter region are significantly associated with allergic sensitization and serum IgE levels. In addition, cultures of activated PBMCs from individuals homozygous for the associated polymorphisms produced increased levels of the Th2 cytokines, IL-4, IL-5, and IL-13, as well as TNF-alpha compared with controls. One of the polymorphisms, -1413G/A, demonstrated differential NF-kappaB binding in mobility shift analysis, suggesting that this polymorphism has functional consequences. Overall, these data demonstrate that ICOS is a susceptibility gene for allergic sensitization, perhaps through the promotion of Th2 differentiation.
ICOS作为Th2细胞发育和效应功能的重要调节因子，这使得ICOS基因座成为Th2介导疾病（如哮喘和过敏）的一个有吸引力的候选基因。在对人类该候选基因座的评估中，我们鉴定出11个变体，并确定推定启动子区域中的两个变体与过敏致敏和血清IgE水平显著相关。此外，与对照组相比，来自相关多态性纯合个体的活化外周血单核细胞培养物产生的Th2细胞因子IL-4、IL-5和IL-13以及TNF-α水平升高。其中一个多态性位点-1413G/A在迁移率变动分析中显示出不同的NF-κB结合，表明该多态性具有功能后果。总体而言，这些数据表明ICOS可能通过促进Th2分化而成为过敏致敏的易感基因。
