MATERNAL AND NEONATAL IMMUNITY

母体和新生儿的免疫力

• 批准号: 2638486
• 负责人: THOMAS B TOMASI
• 金额: $ 28.25万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2638486
• 关键词: DNA footprinting; MHC class II antigen; gene expression; gene induction /repression; gene mutation; genetic promoter element; genetic regulatory element; genetic transcription; immunoregulation; laboratory mouse; molecular cloning; newborn animals; nucleic acid sequence; pregnancy immunology; tissue /cell culture; transcription factor; transfection; trophoblast

The failure of the trophoblast to express MHC class II antigens is believed to be essential for survival of the fetus during pregnancy. It is therefore likely that strong evolutionary pressures to preserve reproduction would develop tight overlapping regulatory controls. We have identified two such control mechanisms which inhibit trophoblast class II expression. An upstream negative regulatory element (IAalphaNRE) in the promoter of the murine class II IAalpha gene that represses transcription specifically in trophoblasts. In addition, the class II transcription activator (CIITA), the master regulator of class II expression is not transcribed in trophoblast cells, nor can it be induced by IFN-gamma or other cytokines that upregulate class II in most other cell types. The goals of this grant are to further define the underlying mechanisms responsible for the inability of the trophoblast to express class II and the physiological relevance of this to fetal persistence. Hopefully, these studies will also elucidate fundamental control mechanisms for class II expression that have application to other areas of clinical relevance such as cancer and autoimmunity.

滋养层不能表达MHCII类抗原， 被认为对怀孕期间胎儿的生存至关重要。 因此，很可能是强大的进化压力， 生殖将形成严格的重叠监管控制。 我们 已经确定了两种这样的控制机制， II类表达。上游负调控元件 在鼠II类IA α基因的启动子中， 特异性抑制滋养层的转录。 此外该 II类转录激活因子（CIITA），II类转录激活因子的主要调节因子， II表达在滋养层细胞中不转录， 由IFN-γ或其他细胞因子诱导，在大多数情况下， 其他细胞类型。 该补助金的目标是进一步确定 滋养层细胞无法在体内 表达II类和这对胎儿的生理相关性 坚持不懈 希望这些研究也能阐明 II类表达的控制机制， 其他临床相关领域，如癌症和自身免疫。