Zhong Weixue, Fei Min, Zhu Yibei, Zhang Xueguang
Institute of Biotechnology and Clinical Immunology Research Laboratory of Jiangsu Province, Soochow University, Suzhou, PR China.
Cell Mol Biol Lett. 2009;14(4):587-608. doi: 10.2478/s11658-009-0023-3. Epub 2009 Jun 25.
Dendritic cells (DC) are professional antigen-presenting cells capable of initiating primary immune responses. They have been intensively studied and are used in both basic immunology research and clinical immunotherapy. However, the genetic pathways leading to DC differentiation and maturation remain poorly understood. Using focused microarrays with oligonucletotide probes for 120 genes encoding co-stimulatory molecules, chemokines, chemokine receptors, cytokines, cytokine receptors, TLRs, and several other related molecules, we analyzed the kinetics of gene expression for the overall differentiation process of monocytes into mature DC. In parallel, we compared the transcriptional profiles in DC maturation in the presence of LPS, TNF-alpha or trimeric CD40L. We found similar transcriptional profiles for early immature DC and immature DC, respectively generated by culturing monocytes with GM-CSF and IL-4 for three or six days. We identified sets of common and stimuli-specific genes, the expression of which changed following stimulation with LPS, TNF-alpha or CD40L. A dynamic analysis of the entire DC differentiation and maturation process showed that some important inflammatory and constitutive chemokines are transcribed in both immature and mature DC. The correlative expression kinetics of the gene pairs IL1R1/IL1R2, IL15/IL15RA, DC-SIGN/ICAM-2 and DC-SIGN/ICAM-3 imply that they all play crucial roles in mediating DC functions. Thus, our analysis with focused microarrays shed light on the transcriptional kinetics of DC differentiation and maturation, and this method may also prove useful for identifying novel marker genes involved in DC functions.
树突状细胞（DC）是能够启动初级免疫反应的专职抗原呈递细胞。它们已得到深入研究，并应用于基础免疫学研究和临床免疫治疗。然而，导致DC分化和成熟的遗传途径仍知之甚少。我们使用针对120个编码共刺激分子、趋化因子、趋化因子受体、细胞因子、细胞因子受体、Toll样受体（TLR）及其他一些相关分子的基因的寡核苷酸探针聚焦微阵列，分析了单核细胞向成熟DC整体分化过程中的基因表达动力学。同时，我们比较了在存在脂多糖（LPS）、肿瘤坏死因子-α（TNF-α）或三聚体CD40配体（CD40L）的情况下DC成熟过程中的转录谱。我们发现，分别通过用粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）培养单核细胞三天或六天产生的早期未成熟DC和未成熟DC具有相似的转录谱。我们鉴定出了一组共同基因和刺激特异性基因，其表达在受到LPS、TNF-α或CD40L刺激后发生了变化。对整个DC分化和成熟过程的动态分析表明，一些重要的炎症性和组成性趋化因子在未成熟和成熟DC中均有转录。基因对IL1R1/IL1R2、IL15/IL15RA、DC-SIGN/ICAM-2和DC-SIGN/ICAM-3的相关表达动力学表明，它们在介导DC功能中均发挥关键作用。因此，我们使用聚焦微阵列进行的分析揭示了DC分化和成熟的转录动力学，并且该方法可能也有助于鉴定参与DC功能的新型标记基因。
