CD14, a key candidate gene associated with a specific immune response to cockroach.
CD14, a key candidate gene associated with a specific immune response to cockroach.
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DOI：
10.1111/j.1365-2222.2010.03561.x
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Barnes KC
中科院分区：
文献类型：
--
作者：
Gao P;Grigoryev DN;Rafaels NM;Mu D;Wright JM;Cheadle C;Togias A;Beaty TH;Mathias RA;Schroeder JT;Barnes KC
对蟑螂过敏原的敏感性是哮喘发病率最强的预测因素之一，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异性反应。我们利用共培养细胞的高通量表达谱研究了共培养的浆细胞样 DC (pDC) 和 CD4+ T 细胞的 Th1/Th2 细胞因子谱，以及对蟑螂抗原的免疫反应的“转录特征”。当培养物暴露于粗制蟑螂抗原时，我们观察到 IL-13、IL-10 和 TNF-α 水平显着升高，但 IL-12p70 和 IFN-α 水平检测不到。在蟑螂过敏和非过敏个体之间观察到 IL-13 存在显着差异 (p = 0.039)。微阵列分析表明，与 4 小时相比，48 小时的反应更大，蟑螂抗原处理的细胞中有 50 个基因独特表达，包括 CD14、S100A8、CCL8 和 IFI44L。在纯化的 pDC、人单核 THP-1 细胞以及暴露于蟑螂提取物的共培养 pDC 和 CD4+ T 细胞的上清液中，进一步观察到 CD14 表达增加。此外，蟑螂过敏和非蟑螂过敏之间 CD14 的表达差异最大，仅在具有 CD14 -260C/T CC“高风险”基因型的个体中观察到。 Ingenuity Pathways Analysis (IPA) 分析表明干扰素信号传导是最重要的经典途径。我们的结果表明，这些差异表达的基因，特别是 CD14 和干扰素信号通路中的基因可能是进一步研究它们在蟑螂过敏原免疫反应中的作用的重要候选基因。
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 DCs (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-α, but undetectable levels of IL-12p70 and IFN-α, 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 hours compared to 4 hours, 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 supernatant of co-cultured pDCs and CD4+ T cells in 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 (IPA) analyses suggested the interferon-signaling as the most significant canonical pathway. Our results suggest these differentially expressed genes, particularly CD14, and genes in the interferon-signaling pathway may be important candidates for further investigation of their role in the immune response to cockroach allergen.
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