Department of Medicine, Division of Allergy and Clinical Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA.
Clin Exp Allergy. 2010 Sep;40(9):1353-64. doi: 10.1111/j.1365-2222.2010.03561.x. Epub 2010 Jul 4.
Sensitization to cockroach allergen is one of the strongest predictors of asthma morbidity, especially among African Americans.
Our aims were to determine the genomic basis of cockroach sensitization and the specific response to cockroach antigen.
We investigated the Th1/Th2 cytokine profile of co-cultured plasmacytoid dendritic cells (pDCs) and CD4+ T cells and the 'transcript signature' of the immune response to cockroach antigen using high-throughput expression profiling of co-cultured cells.
We observed significantly elevated levels of IL-13, IL-10, and TNF-alpha, but undetectable levels of IL-12p70 and IFN-alpha, when cultures were exposed to crude cockroach antigen. A significant difference was observed for IL-13 between cockroach-allergic and non-allergic individuals (P=0.039). Microarray analyses demonstrated a greater response at 48 h compared with 4 h, with 50 genes being uniquely expressed in cockroach antigen-treated cells, including CD14, S100A8, CCL8, and IFI44L. The increased CD14 expression was further observed in purified pDCs, human monocytic THP-1 cells, and the supernatant of co-cultured pDCs and CD4+ T cells on exposure to cockroach extract. Furthermore, the most differential expression of CD14 between cockroach allergy and non-cockroach allergy was only observed among individuals with the CC 'high-risk' genotype of the CD14-260C/T. Ingenuity Pathways Analysis analyses suggested the IFN signalling as the most significant canonical pathway.
Our results suggest that these differentially expressed genes, particularly CD14, and genes in the IFN signalling pathway may be important candidates for further investigation of their role in the immune response to cockroach allergen.
蟑螂过敏原致敏是哮喘发病率的最强预测因素之一，尤其是在非裔美国人中。
我们的目的是确定蟑螂致敏的基因组基础和对蟑螂抗原的特定反应。
我们使用共培养细胞的高通量表达谱来研究共培养的浆细胞样树突状细胞（pDC）和 CD4+T 细胞的 Th1/Th2 细胞因子谱和对蟑螂抗原的免疫反应的“转录特征”。
当培养物暴露于粗蟑螂抗原时，我们观察到 IL-13、IL-10 和 TNF-α的水平显著升高，而 IL-12p70 和 IFN-α的水平无法检测到。蟑螂过敏和非过敏个体之间的 IL-13 水平存在显著差异（P=0.039）。微阵列分析表明，48 小时的反应大于 4 小时，50 个基因在蟑螂抗原处理的细胞中特异表达，包括 CD14、S100A8、CCL8 和 IFI44L。在纯化的 pDC、人单核细胞 THP-1 细胞和共培养的 pDC 和 CD4+T 细胞的上清液中，CD14 的表达在暴露于蟑螂提取物时进一步增加。此外，仅在 CD14-260C/T 的 CC“高风险”基因型个体中观察到蟑螂过敏与非蟑螂过敏之间 CD14 的差异表达最为明显。通路分析表明 IFN 信号通路是最显著的经典通路。
我们的结果表明，这些差异表达的基因，特别是 CD14 和 IFN 信号通路中的基因，可能是进一步研究其在蟑螂过敏原免疫反应中的作用的重要候选基因。
