Liu Sue M, Xavier Ramnik, Good Kim L, Chtanova Tatyana, Newton Rebecca, Sisavanh Mary, Zimmer Sabine, Deng Chaoyang, Silva Diego G, Frost Melinda J, Tangye Stuart G, Rolph Michael S, Mackay Charles R
Immunology and Inflammation Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Sydney 2010, Australia.
J Allergy Clin Immunol. 2006 Aug;118(2):496-503. doi: 10.1016/j.jaci.2006.04.040. Epub 2006 Jun 21.
The precise function of various resting and activated leukocyte subsets remains unclear. For instance, mast cells, basophils, and eosinophils play important roles in allergic inflammation but also participate in other immunologic responses. One strategy to understand leukocyte subset function is to define the expression and function of subset-restricted molecules.
To use a microarray dataset and bioinformatics strategies to identify novel leukocyte markers as well as genes associated with allergic or innate responses.
By using Affymetrix microarrays, we generated an immune transcriptome dataset composed of gene profiles from all of the major leukocyte subsets, including rare enigmatic subsets such as mast cells, basophils, and plasma cells. We also assessed whether analysis of genes expressed commonly by certain groups of leukocytes, such as allergic leukocytes, might identify genes associated with particular responses.
Transcripts highly restricted to a single leukocyte subset were readily identified (>2000 subset-specific transcripts), many of which have not been associated previously with leukocyte functions. Transcripts expressed exclusively by allergy-related leukocytes revealed well known as well as novel molecules, many of which presumably contribute to allergic responses. Likewise, Nearest Neighbor Analysis of genes coexpressed with Toll-like receptors identified genes of potential relevance for innate immunity.
Gene profiles from all of the major human leukocyte subsets provide a powerful means to identify genes associated with single leukocyte subsets, or different types of immune response.
A comprehensive dataset of gene expression profiles of human leukocytes should provide new targets or biomarkers for human inflammatory diseases.
各种静息和活化白细胞亚群的确切功能尚不清楚。例如,肥大细胞、嗜碱性粒细胞和嗜酸性粒细胞在过敏性炎症中起重要作用,但也参与其他免疫反应。了解白细胞亚群功能的一种策略是确定亚群限制性分子的表达和功能。
利用微阵列数据集和生物信息学策略来识别新型白细胞标志物以及与过敏或先天性反应相关的基因。
通过使用Affymetrix微阵列,我们生成了一个免疫转录组数据集,该数据集由所有主要白细胞亚群的基因谱组成,包括罕见的神秘亚群,如肥大细胞、嗜碱性粒细胞和浆细胞。我们还评估了对某些白细胞组(如过敏性白细胞)共同表达的基因进行分析是否可能识别出与特定反应相关的基因。
很容易识别出高度局限于单个白细胞亚群的转录本(>2000个亚群特异性转录本),其中许多以前与白细胞功能无关。仅由过敏相关白细胞表达的转录本揭示了已知的以及新的分子,其中许多可能有助于过敏反应。同样,与Toll样受体共表达基因的最近邻分析确定了与先天免疫潜在相关的基因。
所有主要人类白细胞亚群的基因谱为识别与单个白细胞亚群或不同类型免疫反应相关的基因提供了有力手段。
人类白细胞基因表达谱的综合数据集应为人类炎症性疾病提供新的靶点或生物标志物。