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家族提供了一种新型的脂质抗原抗原系统，该系统与MHC I类或II类分子不同。尽管大鼠和小鼠中不存在1组CD1（CD1A，CD1B和CD1C），但第2组CD1D已通过哺乳动物进化来保存，包括小鼠，大鼠，兔子，绵羊和人类。 CD1D分子由多种器官表达，在肠上皮，肝细胞，表皮细胞以及胸腺细胞和血压细胞中的强烈表达。从系统发育的角度来看，一些研究者假设CD1D分子在各种哺乳动物免疫系统中具有相似的功能意义。但是，CD1D在炎症病理基础上的作用尚不完全理解。我们发现，CD1D反应性淋巴细胞富含正常肝脏，并在其肝脏的炎症状态下传播。对动物模型和遗传性人类疾病（Wilson病）中铜重载的详细检查表明，不变的CDR3轴承NKT细胞可以用作严重（暴发）肝炎的标志。在动物模型中，这些细胞直接造成肝细胞的破坏。另一方面，患有轻度过敏性炎症性疾病的蘑菇植物工人经历了先天性炎症细胞的Th2转移和激活，没有CD1D反应性细胞和NKT细胞增加的证据。当肺状况严重（超敏感性肺炎）时，细胞会增加。这些结果表明，CD1D自反应性细胞在炎症性疾病进展中起关键作用。