Koga Yuhki, Matsuzaki Akinobu, Suminoe Aiko, Hattori Hiroyoshi, Hara Toshiro
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Immunol Lett. 2008 Feb 15;116(1):55-63. doi: 10.1016/j.imlet.2007.11.006. Epub 2007 Dec 4.
The expression of cytokine-associated genes in dendritic cells (DCs) derived from umbilical cord blood (UCB) and adult peripheral blood (APB) was comprehensively compared in order to elucidate the difference in DC function between newborns and adults.
Immature DCs were obtained from UCB and APB of healthy human donors. Several cytokines were added to generate mature DCs. Gene expression was compared using cDNA microarray containing 553 cytokine-associated genes. Eleven genes with differential expression were selected and determined their expression levels in DCs by quantitative real-time RT-PCR.
The expression of the Th1 response-related genes (IL-12B and IL-18) and chemokine genes (CXCL9, CXCL13, CCL18 and CCL24) was significantly lower in UCB-DCs than in APB-DC in both maturation states. On the other hand, calgranulins A and B, which are speculated to induce immune tolerance, showed higher expression in UCB-DCs. The expression of cell cycle-related genes (CDC2 and cyclin B1) was significantly higher in UCB-DCs than in APB-DCs, and immature UCB-DCs proliferated more rapidly than immature APB-DCs.
The expression of genes related to immune responses was significantly different between UCB- and APB-DCs, which may cause a decreased DC-mediated immunity and an increased susceptibility to infection in newborns.
全面比较源自脐带血(UCB)和成人外周血(APB)的树突状细胞(DC)中细胞因子相关基因的表达,以阐明新生儿和成人DC功能的差异。
从未受污染的健康人体供体的UCB和APB中获取未成熟DC。添加几种细胞因子以产生成熟DC。使用包含553个细胞因子相关基因的cDNA微阵列比较基因表达。选择11个差异表达基因,并通过定量实时RT-PCR确定它们在DC中的表达水平。
在两种成熟状态下,UCB-DC中与Th1反应相关的基因(IL-12B和IL-18)和趋化因子基因(CXCL9、CXCL13、CCL18和CCL24)的表达均显著低于APB-DC。另一方面,推测可诱导免疫耐受的钙粒蛋白A和B在UCB-DC中表达较高。细胞周期相关基因(CDC2和细胞周期蛋白B1)在UCB-DC中的表达显著高于APB-DC,且未成熟UCB-DC比未成熟APB-DC增殖更快。
UCB-DC和APB-DC之间免疫反应相关基因的表达存在显著差异,这可能导致新生儿DC介导的免疫力下降以及对感染的易感性增加。