Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.
Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.
复制标题
DOI：
10.1371/journal.pone.0097780
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Meuer S
中科院分区：
文献类型：
--
作者：
Schröder-Braunstein J;Gras J;Brors B;Schwarz S;Szikszai T;Lasitschka F;Wabnitz G;Heidtmann A;Lee YS;Schiessling S;Leowardi C;Al-Saeedi M;Ulrich A;Engelke A;Winter J;Samstag Y;Giese T;Meuer S
常驻人固有层免疫细胞在宿主防御中充当强大的效应器。在这些细胞中与肠道炎症反应的启动相关的分子事件在很大程度上是未知的。在这里，我们的目的是表征表型和功能的变化，诱导这些细胞在肠道炎症发作时，使用人类肠道器官培养模型。在该模型中，健康人结肠粘膜通过EDTA处理耗尽上皮细胞。在上皮层丧失后，如通过qRT-PCR和免疫组织学测定的，在固有层细胞中原位快速诱导炎性介质IL 1B、IL 6、IL 8、IL 23 A、TNFA、CXCL 2和表面受体CD 14、TLR 2、CD 86、CD 54的表达。通过激光捕获显微切割获得的固有层细胞的基因微阵列分析提供了在这些细胞中的肠道炎症反应的起始期间发生的基因表达的全球变化的概述。生物信息学分析深入了解了介导这种炎症反应的信号通路。此外，与已发表的微阵列数据集的炎症粘膜在体内（溃疡性结肠炎）的比较，揭示了一个显着重叠的差异调节基因强调在体内相关的器官培养模型。此外，使用该模型鉴定了以前从未与肠道炎症相关的基因。所表征的器官培养模型可能有助于研究正常粘膜中肠道炎症反应启动的分子机制以及炎症性肠道疾病中这种反应的潜在改变。
Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis) revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.
登录
查看更多内容
T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6
作者：
Autschbach, F;Braunstein, J;Meuer, SC
通讯作者：
Meuer, SC
影响因子：
2.2
作者：
Carrasco, Anna;Mane, Josep;Esteve, Maria
通讯作者：
Esteve, Maria
影响因子：
15.9
作者：
BULL, DM;BOOKMAN, MA
通讯作者：
BOOKMAN, MA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y