权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pathophysiological role of CD1d in organ-specific inflammation

CD1d 在器官特异性炎症中的病理生理学作用

基本信息

批准号：
13470054
负责人：
MATSUURA Akihiro
金额：
$ 8.64万
依托单位：
Fujita Health University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

The non-MHC-encoded CD1 family provides a novel lipid antigen-presenting system that is distinct from either MHC class I or class II molecules. Whereas the group 1 CD1 (CD1a, CD1b and CD1c) were absent in rats and mice, the group 2 CD1d has been conserved through mammalian evolution including mice, rats, rabbits, sheep, and humans. CD1d molecules are expressed by a wide variety of organs, appearing strongly in the intestinal epithelium, hepatocytes, epidermal cells, and to a lesser extent in thymocytes and hematolymphoid cells. From a phylogenetic standpoint, several investigators have hypothesized that CD1d molecules have a similar functional significance in various mammalian immune systems. However, roles of CD1d in pathological basis of inflammation is not fully understand. We find, that CD1d-reactive lymphocytes are enriched in the normal liver and propagated in its inflammatory condition of liver. Detailed examination of the copper overload in an animal model and inherited human disorder (Wilson disease) revealed that that invariant CDR3 bearing NKT cells can be used as a marker of severe (fulminant) hepatitis. In the animal model, these cells directly contribute destruction of hepatocytes. On the other hand, mushroom plant workers with mild allergic inflammatory disorder of the lung experience a Th2 shift and activation of innate inflammatory cells, no evidence of increase of CD1d reactive cells and NKT cells. When the lung status become severe (hypersensitive pneurnonitis), the cells are increased. These results suggest that CD1d self reactive cells play critical roles in progression of inflammatory disorders.

非MHC编码的CD1家族提供了一种不同于MHC I类或II类分子的新型脂质抗原呈递系统。尽管第1组CD1（CD1a、CD1b和CD1c）在大鼠和小鼠中不存在，但第2组CD1d在包括小鼠、大鼠、兔、绵羊和人类在内的哺乳动物进化过程中一直是保守的。CD1d分子由多种器官表达，在肠上皮、肝细胞、表皮细胞中强烈表达，在胸腺细胞和血淋巴样细胞中表达程度较低。从系统发育的角度来看，一些研究人员假设，CD1d分子在各种哺乳动物免疫系统中具有相似的功能意义。然而，CD1d在炎症的病理基础中的作用还不完全清楚。我们发现，CD1d反应性淋巴细胞在正常肝脏中富集，并在肝脏炎症状态下增殖。对动物模型和遗传性人类疾病（威尔逊病）中铜过载的详细检查显示，携带恒定CDR 3的NKT细胞可用作重度（暴发性）肝炎的标志物。在动物模型中，这些细胞直接导致肝细胞的破坏。另一方面，蘑菇厂工人与轻度过敏性炎症性疾病的肺部经验的Th2移位和激活的先天性炎症细胞，没有证据表明增加的CD1d反应性细胞和NKT细胞。当肺的状态变得严重（过敏性肺炎），细胞增加。这些结果表明，CD1d自身反应细胞在炎症性疾病的进展中起着关键作用。